The steroid receptor RNA activator is a functional RNA suspected to participate in the mechanisms underlying breast tumor progression. This RNA is also able to encode for a protein, Steroid Receptor RNA Activator Protein (SRAP), whose exact function remains to be determined. Our aim was to assess, in a large breast cancer cohort, whether levels of this protein could be associated with outcome or established clinical parameters. Following antibody validation, SRAP expression was assessed by tissue-microarray (TMA) analysis of 372 breast tumors. Clinical follow-up and parameters such as steroid receptor and node status were available for all the corresponding cases. Immunohistochemical scores were independently determined by three investigators and averaged. Statistical analyses were performed using standard univariate and multivariate tests. SRAP levels were significantly (Mann-Whitney rank sum test, P | 0.05) higher in estrogen receptor-alpha positive (ER+, n = 271), in progesterone receptor positive

The long noncoding RNA, TINCR, functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in gastric cancer Zhaoliang Chen,1 Hong Liu,1 Huili Yang,1 Yukai Gao,1 Gongwen Zhang,1 Jiaojiao Hu2 1Department of Oncology, Binzhou Central Hospital, Binzhou, Shandong, 2Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, China Background: Accumulating evidence indicates that the long noncoding RNA, TINCR, plays a critical role in cancer progression and metastasis. However, the overall biological role and mechanisms of TINCR that were involved in human gastric cancer (GC) progression remain largely unknown.Methods: TINCR expression was measured in 56 paired tumor and adjacent nontumor tissue samples by real-time polymerase chain reaction (PCR). Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays. The effects of TINCR and miR-375 on GC cell apoptosis and proliferation were studied by RNA

Several years ago, I posted a blog about long noncoding RNAs (lncRNAs), which are defined as non-protein coding transcripts in the range of ~200 nt to ~100 kb long. Interest in lncRNA is driven in large part by a collective scientific desire to uncover and understand the existence and function of all forms of RNA dark matter, so named by analogy to dark energy in cosmology. The lncRNA component of RNA dark matter is certainly generated from transcription of noncoding (formerly junk) DNA, but much has yet to be elucidated about function.. Following are tag lines from my Jan 23, 2018 blog titled Long Noncoding RNA (lncRNA) Revisted, which provides some updates on lncRNA dark matter.. ...

TY - JOUR. T1 - Long noncoding RNA complementarity and target transcripts abundance. AU - Zealy, Richard W.. AU - Fomin, Mikhail. AU - Davila, Sylvia. AU - Makowsky, Daniel. AU - Thigpen, Haley. AU - McDowell, Catherine H.. AU - Cummings, James C.. AU - Lee, Edward S.. AU - Kwon, Sang Ho. AU - Min, Kyung Won. AU - Yoon, Je Hyun. PY - 2018/3. Y1 - 2018/3. N2 - Eukaryotic mRNA metabolism regulates its stability, localization, and translation using complementarity with counter-part RNAs. To modulate their stability, small and long noncoding RNAs can establish complementarity with their target mRNAs. Although complementarity of small interfering RNAs and microRNAs with target mRNAs has been studied thoroughly, partial complementarity of long noncoding RNAs (lncRNAs) with their target mRNAs has not been investigated clearly. To address that research gap, our lab investigated whether the sequence complementarity of two lncRNAs, lincRNA-p21 and OIP5-AS1, influenced the quantity of target RNA ...

Long noncoding RNA NEAT1 promotes cell proliferation and invasion by regulating hnRNP A2 expression in hepatocellular carcinoma cells Yuanyi Mang, Li Li, Jianghua Ran, Shengning Zhang, Jing Liu, Laibang Li, Yiming Chen, Jian Liu, Yang Gao, Gang Ren Department of Hepato-Biliary-Pancreatic Surgery, The Calmette Affiliated Hospital of Kunming Medical University, The First Hospital of Kunming, Kunming, Yunnan, People’s Republic of China Abstract: Growing evidence demonstrates that long noncoding RNAs (lncRNAs) are involved in the progression of various cancers, including hepatocellular carcinoma (HCC). The role of nuclear-enriched abundant transcript 1 (NEAT1), an essential lncRNA for the formation of nuclear body paraspeckles, has not been fully explored in HCC. We aimed to determine the expression, roles and functional mechanisms of NEAT1 in the proliferation and invasion of HCC. Based on real-time polymerase chain reaction data, we suggest that NEAT1 is upregulated in HCC tissues compared with

Cardiogenesis processes in human and animals have differential dynamics, suggesting the existence of species-specific regulators during heart development. However, it remains a challenge to discover the human-specific cardiac regulatory genes, given that most coding genes are conserved. Here, researchers at the University of Pittsburgh School of Medicine report the identification of a human-specific long noncoding RNA, Heart Brake LncRNA 1 (HBL1), which regulates cardiomyocyte development from human induced pluripotent stem cells (hiPSCs). Overexpression of HBL1 repressed, whereas knockdown and knockout of HBL1 increased, cardiomyocyte differentiation from hiPSCs. HBL1 physically interacted with MIR1 in an AGO2 complex. Disruption of MIR1 binding sites in HBL1 showed an effect similar to that of HBL1 knockout. SOX2 bound to HBL1 promoter and activated its transcription. Knockdown of SOX2 in hiPSCs led to decreased HBL1 expression and increased cardiomyocyte differentiation efficiency. Thus, HBL1 ...

Long Noncoding RNA (lncRNA) FOXD2-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Regulating MiR-185/AKT Axis - Related articles #918230

Zhang, Liu, Gao, Zhang, Zhang (2019) Long noncoding RNA XIST acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-217 Panminerva medica ...

Expression of the long noncoding RNA (lncRNA) SPRY4-IT1 is low in normal human melanocytes but high in melanoma cells. siRNA knockdown of SPRY4-IT1 blocks melanoma cell invasion and proliferation, and increases apoptosis. To investigate its function further, we affinity purified SPRY4-IT1 from melanoma cells and used mass spectrometry to identify the protein lipin 2, an enzyme that converts phosphatidate to diacylglycerol (DAG), as a major binding partner. SPRY4-IT1 knockdown increases the accumulation of lipin2 protein and upregulate the expression of diacylglycerol O-acyltransferase 2 (DGAT2) an enzyme involved in the conversion of DAG to triacylglycerol (TAG). When SPRY4-IT1 knockdown and control melanoma cells were subjected to shotgun lipidomics, an MS-based assay that permits the quantification of changes in the cellular lipid profile, we found that SPRY4-IT1 knockdown induced significant changes in a number of lipid species, including increased acyl carnitine, fatty acyl chains, and

Long noncoding RNA LINC00978 has been reported to regulate the progression of several human types of cancer, including gastric and breast cancer. However, knowledge on LINC00978 in non‑small cell lung cancer (NSCLC) is limited. In the present study, it was demonstrated that LINC00978 expression was significantly upregulated in NSCLC tissues compared with the adjacent normal tissues. Furthermore, LINC00978 expression was positively correlated with the tumor, node and metastasis stage, and lymph node metastasis in NSCLC patients. Additionally, LINC00978 knockdown significantly inhibited the proliferation, migration and invasion of NSCLC cells while promoting cell apoptosis. In terms of the underlying mechanism, it was demonstrated that LINC00978 served as a competing endogenous RNA sponge for microRNA (miR)‑6754‑5p, which was downregulated in NSCLC tissues. The present study demonstrated that there was a negative correlation between LINC00978 and miR‑6754‑5p expression levels in NSCLC ...

Staphylococcus aureus is a human pathogen causing a variety of diseases by versatile expression of a large set of virulence factors that most prominently features the cytotoxic and hemolytic pore-forming alpha-toxin. Expression of alpha-toxin is regulated by an intricate network of transcription factors. These include two-component systems sensing quorum and environmental signals as well as regulators reacting to the nutritional status of the pathogen. We previously identified the repressor of surface proteins (Rsp) as a virulence regulator. Acute cytotoxicity and hemolysis are strongly decreased in rsp mutants, which are characterized by decreased transcription of toxin genes as well as loss of transcription of a 1,232- nucleotide (nt)-long noncoding RNA (ncRNA), SSR42. Here, we show that SSR42 is the effector of Rsp in transcription regulation of the alpha-toxin gene, hla. SSR42 transcription is enhanced after exposure of S. aureus to subinhibitory concentrations of oxacillin which thus leads ...

Long Noncoding RNA HOTTIP Promotes Nasopharyngeal Cancer Cell Proliferation, Migration, and Invasion by Inhibiting miR-4301 - Order reprints #912728

title: The long noncoding RNA LUCAT1 promotes tumorigenesis by controlling ubiquitination and stability of DNA methyltransferase 1 in esophageal squamous cell carcinoma, doi: 10.1016/j.canlet.2017.12.016, category: Article

Circulating Long Noncoding RNA as a Potential Target for Prostate Cancer. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

Transcriptomic analyses have identified tens of thousands of intergenic, intronic, and cis-antisense long noncoding RNAs (lncRNAs) that are expressed from mammalian genomes. Despite progress in functional characterization, little is known about the post-transcriptional regulation of lncRNAs and their half-lives. Although many are easily detectable by a variety of techniques, it has been assumed that lncRNAs are generally unstable, but this has not been examined genome-wide. Utilizing a custom noncoding RNA array, we determined the half-lives of ∼800 lncRNAs and ∼12,000 mRNAs in the mouse Neuro-2a cell line. We find only a minority of lncRNAs are unstable. LncRNA half-lives vary over a wide range, comparable to, although on average less than, that of mRNAs, suggestive of complex metabolism and widespread functionality. Combining half-lives with comprehensive lncRNA annotations identified hundreds of unstable (half-life | 2 h) intergenic, cis-antisense, and intronic lncRNAs, as well as lncRNAs showing

TY - JOUR. T1 - Long non-coding RNA (lncRNA) transcriptional landscape in breast cancer identifies LINC01614 as non-favorable prognostic biomarker regulated by TGFβ and focal adhesion kinase (FAK) signaling. AU - Vishnubalaji, Radhakrishnan. AU - Shaath, Hibah. AU - Elkord, Eyad. AU - Alajez, Nehad M.. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Long non-coding RNAs (lncRNAs) represent a class of epigenetic regulators implicated in a number of physiological and pathological conditions. Herein, we characterized the lncRNA expression portrait from 837 patients with invasive breast cancer and 105 normals from the cancer genome atlas (TCGA), which revealed eighteen upregulated and forty-six downregulated lncRNAs. Clustering analysis revealed distinct lncRNA profile for the triple negative breast cancer (TNBC) and normal breast tissue, while less separation was observed among the HER2+HR+, HER2+HR−, HER2−HR+ molecular subtypes. LINC01614, and LINC01235 correlated with worse disease-free survival (DFS), ...

The abundance of mammalian long intergenic non-coding RNA (lincRNA) genes is high, yet their functions remain largely unknown. One possible way to study this important question is to use large-scale comparisons of various characteristics of lincRNA with those of protein-coding genes for which a large body of functional information is available. A prominent feature of mammalian protein-coding genes is the high evolutionary conservation of the exon-intron structure. Comparative analysis of putative intron positions in lincRNA genes from various mammalian genomes suggests that some lincRNA introns have been conserved for over 100 million years, thus the primary and/or secondary structure of these molecules is likely to be functionally important.

To evaluate the relevance of our chicken lncRNA set, we analyzed the gene expression profiles of the three classes putative lncRNA transcripts, new mRNAs and ambiguous RNAs and also compared the structural features of our lncRNAs with those of the mouse and human lncRNAs. As expected, the 2193 putative lncRNA genes are on average tenfold less expressed than the known or new protein-coding genes, and the ambiguous RNAs have an intermediate expression (Fig. 1b). This is in accordance with previous findings in mammals that showed that lncRNAs are far less expressed than protein-coding genes [6, 29-31]. Then, we characterized the structural features of these chicken putative lncRNA transcripts in comparison to the human and mouse lncRNAs available in Ensembl and compared them with the protein-coding RNAs available in Ensembl for these three species. Overall, the features observed for the chicken lncRNAs are consistent with those observed in mammals in the human and mouse ENCODE projects [6] ...

Long non-coding RNA HOTAIR exerts regulatory functions in various biological processes in cancer cells, such as proliferation, apoptosis, mobility, and invasion. We previously found that HOX transcript antisense RNA (HOTAIR) is a negative prognostic factor and exhibits oncogenic activity in hepatocellular carcinoma (HCC). In this study, we aimed to investigate the role and molecular mechanism of HOTAIR in promoting HCC cell migration and invasion. Firstly, we profiled its gene expression pattern by microarray analysis of HOTAIR loss in Bel-7402 HCC cell line. The results showed that 129 genes were significantly down-regulated, while 167 genes were significantly up-regulated (fold change |2, p | 0.05). Bioinformatics analysis indicated that RNA binding proteins were involved in this biological process. HOTAIR suppression using RNAi strategy with HepG2 and Bel-7402 cells increased the mRNA and protein expression levels of RNA binding motif protein 38 (RBM38). Moreover, the expression levels of RBM38 in

Long noncoding RNAs (lncRNAs) are key regulators of chromatin state, yet the nature and sites of RNA-chromatin interaction are mostly unknown. Here we introduce Chromatin Isolation by RNA Purification (ChIRP), where tiling oligonucleotides retrieve specific lncRNAs with bound protein and DNA sequenc …

Long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of human cancers, including renal cell carcinoma (RCC). Small nucleolar RNA host gene 4 (SNHG4) is reported to play an essential role in tumor growth and progression. However, the molecular mechanisms and function of SNHG4 in RCC remain undocumented. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine expression levels of SNHG4 in RCC tissue samples and cell lines. Cell counting kit-8, western blotting, activities of caspase-3, -8, and -9, wound-healing, and transwell invasion assays were performed to explore cell proliferation, apoptosis, migration, and invasion. The interaction among SNHG4, miR-204-5p, and RUNX2 was verified by bioinformatic analysis, a luciferase gene report, qRT-PCR, western blot analysis, and RNA immunoprecipitation assays. Xenograft mouse models were carried out to examine the role of SNHG4 in RCC in vivo. SNHG4 was highly expressed in RCC tissue samples and cell lines,

LncRNAs are among the least well-understood of non-protein-coding RNAs. They were previously considered merely transcriptional noise [11] but have increasingly garnered attention in recent years. Newer studies have shown that lncRNAs are involved in EMT. For example, several lncRNAs can be involved in the regulation or activation of the WNT signaling pathway in the Twist-induced EMT process [20]. H19 can promote pancreatic cancer metastasis by derepressing let-7s suppression on its target HMGA2-mediated EMT [21]. However, to our knowledge, no previous study has focused on the microarray expression profile of lncRNAs in LECs during EMT. Thus, we conducted the current study to assess the role of lncRNAs in the development and progression of EMT in LECs from the perspective of lncRNA.. In this study, we chose the HLE B-3 cell line. It is a primary cell line of LECs that is immortalized via infection with an adenovirus 12-SV40 virus, and can be used to investigate HLE physiology and cataracts ...

Accumulating evidence indicates that lncRNAs may have potential as new biomarkers to predict prognosis of different human cancers. HOTAIR lncRNA, transcribed from the human HOX locus, has been suggested to regulate gene expression of important target genes and up-regulation has been noted in malignancies. The role of HOX transcript antisense RNA in acute myeloid leukemia (AML) was investigated in the present case control study. HOTAIR expression was evaluated in blood samples of twenty five de novo AML patients and fifty healthy controls using real-time quantitative reverse transcription-PCR (qRT-PCR). Our results demonstrated no significant differences in HOTAIR lncRNA expression level between AML patients and healthy individuals. The obtained data indicate that HOTAIR is not an informative and reliable biomarker for AML diagnosis, although our results should be confirmed in further studies.

Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. The prognosis of ESCC remains poor; thus, it is still necessary to further dissect the underlying mechanisms and explore therapeutic targets of ESCC. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. Some lncRNAs, such as HOTAIR and POU3F3, were reported to play important roles in ESCC. Here, we characterized the expression profile of taurine-upregulated gene 1 (TUG1), a lncRNA recruiting and binding to polycomb repressive complex 2 (PRC2), in ESCC. In a cohort of 62 patients, TUG1 was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues, and high expression level of TUG1 was associated with family history and upper segment of esophageal cancer (p , 0.05). Further, in vitro silencing TUG1 via siRNA inhibited the proliferation and migration of ESCC cells and ...

CTD-2020K17.1, a Novel Long Non-Coding RNA, Promotes Migration, Invasion, and Proliferation of Serous Ovarian Cancer Cells In Vitro - Order reprints #908456

The role of long noncoding RNAs (lncRNAs) in acute myeloid leukemia (AML) is becoming increasingly concerned. Previous studies have reported that the lncRNA small nucleolar RNA host gene 1 (SNHG1) is involved in multiple human malignant tumors, while its expression and role in AML is still unexplored. Here, we show that SNHG1 is highly expressed in AML specimens from non-M3 patients, as well as AML cell lines. Meanwhile, upregulation of SNHG1 is correlated with poor prognosis. Notably, SNHG1 facilitates the proliferation and inhibits the apoptosis of AML cells in vitro. Consistent with these findings, knockdown of SNHG1 significantly inhibits AML progression in an immunodeficient mouse model. Mechanistically, we found that an anti-tumor microRNA-101 (miR-101) is upregulated and its target genes are downregulated in AML cells after SNHG1 knockdown. Further investigations display that SNHG1 can serve as a competing endogenous RNA (ceRNA) to inhibit miR-101. In conclusion, our data indicate that ...

Long noncoding RNAs (lncRNAs) have emerged as important regulators in the development and progression of gastric cancer (GC). ARHGAP27P1 is a pseudogene-derived lncRNA, and it has been found to be associated with GC in our preliminary study, but this association has not been studied further. Herein, we confirmed that ARHGAP27P1 was significantly downregulated in GC tissues, plasma and cells. Low expression of ARHGAP27P1 was closely associated with advanced TNM stage, increased invasion depth and lymphatic metastasis. Low ARHGAP27P1 expression also predicted a poor prognosis in GC patients. Functionally, overexpression of ARHGAP27P1 inhibited proliferation, invasion, and migration in GC cells, while silencing of ARHGAP27P1 showed the opposite effects. Mechanistic investigations showed that ARHGAP27P1 had a key role in G0/G1 arrest. We further demonstrated that ARHGAP27P1 was associated with Jumonji-domain containing 3 (JMJD3) and that this association was required for the demethylation of H3K27me3,

Full Text - Transforming growth factor-β1 (TGFβ1)-induced differentiation into and the activation of myofibroblasts have been regarded as critical events in benign prostatic hyperplasia (BPH); however, the underlying mechanisms of BPH pathogenesis remain unclear. Microarray profiling, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Gene Ontology (GO) enrichment analysis were performed to confirm the candidate genes and long non-coding RNA (lncRNAs) related to BPH. Collagen Type III (COL3A1) was significantly upregulated by TGFβ1 in prostate stromal cells (PrSCs) and might be involved in DNM3OS function in myofibroblasts upon TGFβ1 stimulation. Upon TGFβ1 stimulation, COL3A1 protein was decreased by DNM3OS silencing. miR-29a and miR-29b could directly bind to the DNM3OS and COL3A1 3' untranslated region (UTR)s to negatively regulate their expression, and by serving as a competing endogenous RNAs (ceRNA), DNM3OS competed with

The human genome encodes thousands of long non-coding RNAs (lncRNAs), the majority of which are poorly conserved and uncharacterized. Here we identify a primate-specific lncRNA (CHROME), elevated in the plasma and atherosclerotic plaques of individuals with coronary artery disease, that regulates cellular andsystemic cholesterol homeostasis. LncRNA CHROME expression is influenced by dietary and cellular cholesterol via the sterol-activated liver X receptor transcription factors, which control genes mediating responses to cholesterol overload. Using gain- and loss-of-function approaches, we show that CHROME promotes cholesterol efflux and HDL biogenesis by curbing the actions of a set of functionally related microRNAs that repress genes in those pathways. CHROME knockdown in human hepatocytes and macrophages increases levels of miR-27b, miR-33a, miR-33b and miR-128, thereby reducing expression of their overlapping target gene networks and associated biologic functions. In particular, cells lacking CHROME

The noncoding form of the steroid receptor RNA activator (SRA, AF092038, http://annolnc.cbi.pku.edu.cn/cases/SRA) has been reported to function as a noncoding RNA by Lanz et al. [41] and is the first lncRNA that has experimentally derived secondary structure, which was derived by Novikova et al. [42]. In the interactive secondary structure plot with vertebrate phyloP score as color overlay, it is easy to identify two conserved regions. One is a hairpin region from base 30 to 72 (Fig. 3a). With approximately 75% of bases colored red, this conserved sub-structure is clearly distinguishable from others. In fact, this region corresponds to the most conserved H2 sub-structure highlighted by Novikova et al. [42]. Site-directed mutagenesis of this region reduced the co-activation performance of SRA by 40% [43], suggesting the importance of lncRNA secondary structure on its function [44]. The other distinct region is a three-way junction hairpin sub-structure from base 506 to 555 with 78% colored red ...

Aberrations in long noncoding RNA (lncRNA) expression have been recognized in numerous human diseases. In the present study, the of role the long noncoding RNA HOX antisense intergenic RNA myeloid 1 variant (HOTAIRM1‑1) in regulating the pathological progression of osteoarthritis (OA) was investigated. The aberrant expression of HOTAIRM1‑1 in OA was demonstrated, but the molecular mechanisms require further analysis. The aim of the present study was to explore the function of miR‑125b in modulating chondrocyte viability and apoptosis, and to address the functional association between HOTAIRM1‑1 and miR‑125b as potential targets. A miR‑125b inhibitor was used, which laid the foundation for the following investigation. The study confirmed that HOTAIRM1‑1 and miR‑125b are inversely expressed in chondrocytes. The expression of HOTAIRM1‑1 was downregulated and the expression of miR‑125b was upregulated in tissues from patients with OA. HOTAIRM1‑1 directly interacted with ...

Colorectal cancer (CRC) is one of the most common types of cancer worldwide. However, the molecular mechanisms involved in CRC initiation and progression is remained to be unknown. It seems that lncRNAs, as the main and lengthy functional transcripts of the genome, have important roles in different cancers such as CRC. CRC-related lncRNAs are reported to be involved in diverse molecular processes such as metastasis, invasion, cell proliferation, and apoptosis. This study was aimed to analyse the expression level of lncRNA SNHG1 in colorectal adenocarcinoma and normal tissues. We performed an in silico analysis on a large cohort and confirmed the results by experimental analysis of clinical samples through real-time PCR. Our findings demonstrated that that SNHG1 is potentially overexpressed in tumor tissues compared with adjacent normal tissues. The expression level of SNHG1 was shown to be potentially associated with clinicopathological features of tumors. The current study suggests the potential role

Researchers have found a set of long non-coding RNAs (lncRNAs) - RNA molecules with no protein-coding capacity - that participate in the metastatic process of ovarian cancer cells.. Inhibiting one of these molecules, called DNM3OS, reduced migration and invasion, suggesting that targeting lncRNAs might be a viable approach for treating ovarian cancer.. The study, Decoding critical long non-coding RNA in ovarian cancer epithelial-to-mesenchymal transition, was published in the journal Nature Communications.. Metastasis, which refers to the spread of cancer cells, is a common occurrence in patients with ovarian cancer and occurs in as many as 80 percent of patients. Metastasis is dependent on the ability of cancer cells to undergo a process called epithelial-to-mesenchymal transition (EMT), which allows cells to detach from other cancer cells and enter circulation.. Recent studies have suggested that lncRNAs are involved in the metastatic process. These molecules are known to regulate gene ...

Hepatocellular carcinoma (HCC) is a common malignant tumor with high fatality rate. Recent studies reported that up-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was found in HCC tissues, and which could affect HCC cells biological processes. However, the potential molecular mechanism of ANRIL in HCC is still unclear. The study aimed to uncover the effect of ANRIL on HepG2 cells growth, migration and invasion. The knockdown expression vectors of ANRIL were transfected into HepG2 cells, and qRT-PCR, CCK-8, flow cytometry, Transwell and western blot assays were performed to analyze the effect of ANRIL on cell proliferation, apoptosis, migration and invasion. The relative expression of miR-191 was then examined in ANRIL knockdown vector transfected cells. These experiments were repeated again for exploring the effect of miR-191 on HepG2 cells. NF-κB and Wnt/β-catenin signaling pathways were examined by using western blot assay. Knockdown of ANRIL inhibited

The steroid receptor RNA activator gene (SRA1) generates two distinct entities. SRA RNA coactivates several NRs whereas SRA protein (SRAP) is suspected to regulate the activity of several transcription factors, including estrogen receptors (ER). Splicing of SRA intron-1 is the major event defining SRAP coding frame. Fully spliced, coding SRA and intron-1 retained, non-coding SRA coexist in breast cancer cells. The relative proportion between the two types of SRA RNA maintains a balance between two genetically linked entities, SRA and SRAP. In this study, a minigene model was used to demonstrate that the primary sequence of SRA exon-1-intron-1-exon-2 is sufficient for alternative splicing of SRA intron-1. In addition, a modified oligoribonucleotidic construct promotes SRA intron-1 retention in breast cancer cells. This oligoribonucleotide differentially alters estradiol-induced transcription of ER regulated genes. Together, results presented herein demonstrate that the SRA-SRAP balance, which can ...

Long non-coding RNAs (lncRNAs), representing a large proportion of non-coding transcripts across the human genome, are evolutionally conserved and biologically functional. At least one-third of the phenotype-related loci identified by genome-wide association studies (GWAS) are mapped to non-coding intervals. However, the relationships between phenotype-related loci and lncRNAs are largely unknown. Utilizing the 1000 Genomes data, we compared single-nucleotide polymorphisms (SNPs) within the sequences of lncRNA and protein-coding genes as defined in the Ensembl database. We further annotated the phenotype-related SNPs reported by GWAS at lncRNA intervals. Because prostate cancer (PCa) risk-related loci were enriched in lncRNAs, we then performed meta-analysis of two existing GWAS for discovery and an additional sample set for replication, revealing PCa risk-related loci at lncRNA regions. The SNP density in regions of lncRNA was similar to that in protein-coding regions, but they were less ...

TY - JOUR. T1 - The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. AU - Ranzani, Valeria. AU - Rossetti, Grazisa. AU - Panzeri, Ilaria. AU - Arrigoni, Alberto. AU - Bonnal, Raoul J P. AU - Curti, Serena. AU - Gruarin, Paola. AU - Provasi, Elena. AU - Sugliano, Elisa. AU - Marconi, Maurizio. AU - De Francesco, Raffaele. AU - Geginat, Jens. AU - Bodega, Beatrice. AU - Abrignani, Sergio. AU - Pagani, Massimiliano. PY - 2015/2/17. Y1 - 2015/2/17. N2 - Long noncoding RNAs are emerging as important regulators of cellular functions, but little is known of their role in the human immune system. Here we investigated long intergenic noncoding RNAs (lincRNAs) in 13 subsets of T lymphocytes and B lymphocytes by next-generation sequencing-based RNA sequencing (RNA-seq analysis) and de novo transcriptome reconstruction. We identified over 500 previously unknown lincRNAs and described lincRNA signatures. Expression of linc-MAF-4, ...

TY - JOUR. T1 - MALAT1 long non-coding RNA in cancer. AU - Yoshimoto, Rei. AU - Mayeda, Akila. AU - Yoshida, Minoru. AU - Nakagawa, Shinichi. N1 - Funding Information: R.Y. was supported by the research grants from the Hori Information Science Promotion Foundation . Publisher Copyright: © 2015 Elsevier B.V. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.. PY - 2016/1/1. Y1 - 2016/1/1. N2 - A recent massive parallel sequencing analysis has shown the fact that more than 80% of the human genome is transcribed into RNA. Among many kinds of the non-protein coding RNAs, we focus on the metastasis associated lung adenocarcinoma transcript 1 (MALAT1) that is a long non-coding RNA upregulated in metastatic carcinoma cells. Two molecular functions of MALAT1 have been proposed, one is the control of alternative splicing and the other is the transcriptional regulation. In this review, we document the molecular characteristics and functions of MALAT1 and shed light on the implication in the ...

BACKGROUND: Long considered to be the building block of life, it is now apparent that protein is only one of many functional products generated by the eukaryotic genome. Indeed, more of the human genome is transcribed into noncoding sequence than into protein-coding sequence. Nevertheless, whilst we have developed a deep understanding of the relationships between evolutionary constraint and function for protein-coding sequence, little is known about these relationships for non-coding transcribed sequence. This dearth of information is partially attributable to a lack of established non-protein-coding RNA (ncRNA) orthologs among birds and mammals within sequence and expression databases. RESULTS: Here, we performed a multi-disciplinary study of four highly conserved and brain-expressed transcripts selected from a list of mouse long intergenic noncoding RNA (lncRNA) loci that generally show pronounced evolutionary constraint within their putative promoter regions and across exon-intron boundaries. We

Many cancer risk loci act as expression quantitative trait loci (eQTLs) of transcripts including non-coding RNA. Long non-coding RNAs (lncRNAs) are implicated in various human cancers. However, the pathological and clinical impacts of the genetic determinants of lncRNAs in cancers remain largely unknown. In this study, we performed eQTL mapping of lncRNA expression (elncRNA) in 11 TCGA cancer types and characterized the biological processes of elncRNAs in the setting of genomic location, cancer treatment responses, and immune microenvironment. As a result, 10.86% of the cis-eQTLs and 1.67% of the trans-eQTLs of lncRNA were related to known genome-wide association studies (GWAS) cancer risk loci. The elncRNAs are significantly enriched for those which are previously annotated as predictive of drug sensitivities in cancer cell lines. We further revealed the downstream transcriptomic effectors of eQTL-elncRNA pairs. Our data specifically suggested that the genes affected by eQTL-elncRNA associations are

Whilst only approximately 1.06% of the human genome appears to encode protein [1, 2] at least four times this amount is transcribed into stable non-protein-coding RNA (ncRNA) transcripts [3-5]. Unfortunately, the biological relevance of the vast majority of this extensive and interleaving network of coding RNAs and ncRNAs remains far from clear. One possibility is that many ncRNAs result simply from transcriptional noise. If so, their sequence and transcription might be expected not to be conserved outside of restricted phyletic lineages. Indeed, the finding that only 14% of the well-defined mouse long intergenic ncRNAs (lncRNAs) identified in the FANTOM projects [6, 7] have a transcribed ortholog in human (based on analyses of known EST and cDNA data sets) [2] argues against their functionality. Similarly, known human intergenic lncRNA loci are generally not conserved in sequence at statistically significant levels in the mouse genome [3, 8, 9], and there is little evidence for conserved ...

Helicobacter pylori (H.pylori) is a major human pathogenic bacterium in gastric mucosa which is linked to the development of gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. However the regulatory mechanism of H.pylori-induced immune response is not clear. Long non-coding RNA (lncRNA) has recently emerged as key post-transcriptional regulators of gene expression, differentiation. The investigators had a preliminary results which THRIL (TNFα and hnRNPL related immunoregulatory lincRNA) and PACER(p50-associated COX-2 extragenic RNA) played a potential role in H.pylori induced inflammatory cascade. However, there wasnt a previous study about expression of THRIL, PACER in a human tissue. Therefore, the investigators aimed to evaluate the expression of THRIL, PACER in patients with gastrointestinal disease according to H.pylori infection ...

Genomic and transcriptomic data on kiwifruit (Actinidia chinensis) in public databases are very limited despite its nutritional and economic value. Previously, we have constructed and sequenced nine fruit RNA-Seq libraries of A. chinensis

MHM is a chicken Z chromosome-linked locus that is methylated and transcriptionally silent in male cells, but is hypomethylated and transcribed into a long non-coding RNA in female cells. MHM has been implicated in both localised dosage compensation and sex determination in the chicken embryo, but direct evidence is lacking. We investigated the potential role of MHM in chicken embryonic development, using expression analysis and retroviral-mediated mis-expression. At embryonic stages, MHM is only expressed in females. Northern blotting showed that both sense and antisense strands of the MHM locus are transcribed, with the sense strand being more abundant. Whole mount in situ hybridization confirmed that the sense RNA is present in developing female embryos, notably in gonads, limbs, heart, branchial arch and brain. Within these cells, the MHM RNA is localized to the nucleus. The antisense transcript is lowly expressed and has a cytoplasmic localization in cells. Mis-expression of MHM sense and antisense

Alterations in chromatin modulators like the nuclear deubiquitinating enzyme BAP1 are the most frequently observed genetic alterations reported in intrahepatic CCA, yet the molecular mechanisms by which they modulate cancer cell behavior are unknown. BAP1 can act as a tumor suppressor and can regulate several cellular processes through its interaction with other protein partners such as host cell factor 1, O-linked N-acetylglucosamine transferase, transcription factor Ying Yang1, ASXL1/2, and FoxK1/K2 and DNA repair proteins like BRCA1/BARD1 heterodimer and RAD51. In the present study, we identify alterations in long non-coding RNA gene expression as a contributor to tumor cell phenotype and differential therapeutic sensitivity of CCA cells that is related to BAP1 expression.. Alterations in BAP1 expression in other cancers such as renal cell carcinoma, breast carcinoma, small cell and non-small cell lung cancers, malignant mesothelioma, metastasizing uveal melanoma, and hepatic cancers can ...

Long non-coding RNAs (long ncRNAs, lncRNA) are defined as transcripts longer than 200 nucleotides that are not translated into protein. This somewhat arbitrary limit distinguishes long ncRNAs from small non-coding RNAs such as microRNAs (miRNAs), short interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. However, very recent research has shown that some lncRNAs have been misannotated and do in fact encode proteins. A recent study found only one-fifth of transcription across the human genome is associated with protein-coding genes, indicating at least four times more long non-coding than coding RNA sequences. However, it is large-scale complementary DNA (cDNA) sequencing projects such as FANTOM (Functional Annotation of Mammalian cDNA) that reveal the complexity of this transcription. The FANTOM3 project identified ~35,000 non-coding transcripts from ~10,000 distinct loci that bear many signatures of mRNAs, including 5 capping, ...

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its ...

In female mammals, one of the two X chromosomes becomes genetically silenced to compensate for dosage imbalance of X-linked genes between XX females and XY males. X chromosome inactivation (X-inactivation) is a classical model for epigenetic gene regulation in mammals and has been studied for half a century. In the last two decades, efforts have been focused on the X inactive-specific transcript (Xist) locus, discovered to be the master regulator of X-inactivation. The Xist gene produces a non-coding RNA that functions as the primary switch for X-inactivation, coating the X chromosome from which it is transcribed in cis. Significant progress has been made towards understanding how Xist is regulated at the onset of X-inactivation, but our understanding of the molecular basis of silencing mediated by Xist RNA has progressed more slowly. A picture has, however, begun to emerge, and new tools and resources hold out the promise of further advances to come. Here, we provide an overview of the current state of

Emerging evidence indicates that Long non-coding RNAs (LncRNAs) and microRNAs (miRNAs) play crucial roles in tumor progression, including hepatocellular carcinoma (HCC). However, whether there is a crosstalk between LncRNA pituitary tumor-transforming 3 (PTTG3P) and miR-383 in HCC remains unknown. This study is designed to explore the underlying mechanism by which LncRNA PTTG3P sponges miR-383 during HCC progression. qPCR and Western blot were used to analyze LncRNA PTTG3P, miR-383 and other target genes expression. CCK-8 assay was performed to examine cell proliferation. Annexin V-PE/PI and PI staining were used to analyze cell apoptosis and cell cycle distribution by flow cytometry, respectively. Transwell migration and invasion assays were used to examine cell migration and invasion abilities. An in vivo xenograft study was performed to detect tumor growth. Luciferase reporter assay and RNA pull-down assay were carried out to detect the interaction between miR-383 and LncRNA PTTG3P. RIP was carried

Despite the established role of the transcription factor MYC in cancer, little is known about the impact of a new class of transcriptional regulators, the long noncoding RNAs (lncRNAs), on MYC ability to influence the cellular transcriptome. Here, we have intersected RNA-sequencing data from two MYC-inducible cell lines and a cohort of 91 B-cell lymphomas with or without genetic variants resulting in MYC overexpression. We identified 13 lncRNAs differentially expressed in IG-MYC-positive Burkitt lymphoma and regulated in the same direction by MYC in the model cell lines. Among them, we focused on a lncRNA that we named MYC-induced long noncoding RNA (MINCR), showing a strong correlation with MYC expression in MYC-positive lymphomas. To understand its cellular role, we performed RNAi and found that MINCR knockdown is associated with an impairment in cell cycle progression. Differential gene expression analysis after RNAi showed a significant enrichment of cell cycle genes among the genes ...

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by rapid disease progression. The needs for new therapeutic strategies for MCL patients call for further understanding on the molecular mechanisms of pathogenesis of MCL. Recently, long noncoding RNAs (lncRNAs) have been recognized as key regulators of gene expression and disease development, however, the role of lncRNAs in non-Hodgkin lymphoma and specifically in MCL is still unknown. Next generation RNA-sequencing was carried out on MCL patient samples along with normal controls and data was analyzed. As a result, several novel lncRNAs were found significantly overexpressed in the MCL samples with lncRNA ROR1-AS1 the most significant one. We cloned the ROR1-AS1 lncRNA in expression vector and ectopically transfected in MCL cell lines. Results showed that overexpression of ROR1-AS1 lncRNA promoted growth of MCL cells while decreased sensitivity to the treatment with drugs ibrutinib and dexamethasone. ROR-AS1 overexpression also

BACKGROUND: X chromosome inactivation is the mechanism used in mammals to achieve dosage compensation of X-linked genes in XX females relative to XY males. Chromosome silencing is triggered in cis by expression of the non-coding RNA Xist. As such, correct regulation of the Xist gene promoter is required to establish appropriate X chromosome activity both in males and females. Studies to date have demonstrated co-transcription of an antisense RNA Tsix and low-level sense transcription prior to onset of X inactivation. The balance of sense and antisense RNA is important in determining the probability that a given Xist allele will be expressed, termed the X inactivation choice, when X inactivation commences. RESULTS: Here we investigate further the mechanism of Xist promoter regulation. We demonstrate that both sense and antisense transcription modulate Xist promoter DNA methylation in undifferentiated embryonic stem (ES) cells, suggesting a possible mechanistic basis for influencing X chromosome choice.

Cancers of the female reproductive system include ovarian, uterine, vaginal, cervical and vulvar cancers, which are termed gynecologic cancer. The emergence of long noncoding RNAs (lncRNAs), which are believed to play a crucial role in several different biological processes, has made the regulation of gene expression more complex. Although the function of lncRNAs is still rather elusive, their broad involvement in the initiation and progression of various cancers is clear. They are also involved in the pathogenesis of cancers of the female reproductive system. LncRNAs play a critical physiological role in apoptosis, metastasis, invasion, migration and cell proliferation in these cancers. Different expression profiles of lncRNAs have been observed in various types of tumors compared with normal tissues and between malignant and benign tumors. These differential expression patterns may lead to the promotion or suppression of cancer development and tumorigenesis. In the current review, we present the

Recently, studies have revealed that the human genome contains more than 20,000 protein-coding genes and that ,98 % of the total genome can be transcribed to RNAs that do not produce any proteins. These portions of the genome are named non-coding RNA (ncRNA) genes [29]. lncRNAs are ncRNA transcripts greater than 200 nts in length. There are more than 3000 human lncRNAs, but very few of them have been characterized [30, 31]. Although only a few lncRNAs have been characterized in detail, recent studies have revealed that lncRNAs participate in diverse biological processes through distinct mechanisms [32-34]. However, these molecular mechanisms remain incompletely understood. Thus, more studies should be performed to clarify the biological and molecular mechanisms of lncRNAs in cancer [35].. In this study, we evaluated the expression of HOTTIP in glioma tissues. HOTTIP expression was markedly decreased in glioma tissues compared with normal tissues, and the expression of HOTTIP in glioma cell lines ...

TY - JOUR. T1 - Regulation of transcription by long noncoding RNAs. AU - Bonasio, Roberto. AU - Shiekhattar, Ramin. N1 - Publisher Copyright: © 2014 by Annual Reviews. All rights reserved.. PY - 2014/11/23. Y1 - 2014/11/23. N2 - Over the past decade there has been a greater understanding of genomic complexity in eukaryotes ushered in by the immense technological advances in high-throughput sequencing of DNA and its corresponding RNA transcripts. This has resulted in the realization that beyond protein-coding genes, there are a large number of transcripts that do not encode for proteins and, therefore, may perform their function through RNA sequences and/or through secondary and tertiary structural determinants. This review is focused on the latest findings on a class of noncoding RNAs that are relatively large (,200 nucleotides), display nuclear localization, and use different strategies to regulate transcription. These are exciting times for discovering the biological scope and the mechanism ...

The profiling approaches used in this study have led to several novel discoveries in rat genomics, VSMC and Ang II-mediated gene regulation. Because rats are a widely used model organism for research related to CVDs, diabetes mellitus, and other pathologies, it is imperative to analyze their transcriptome in-depth. Our annotation of novel transcripts significantly expands the existing number of known transcripts expressed in the rat genome, which, compared with the human and mouse genomes, remains less well annotated. We found that, similar to mouse and human, the rat genome contains lncRNAs that are less abundantly expressed than previously annotated rat transcripts.22 Notably, our studies revealed that the identified lncRNAs may function as host transcripts for small RNAs, such as miRNAs. Our analysis of the transcriptome and epigenome associated with H3K4me3 and H3K36me3 uncovered that Lnc-Ang362 is proximal to miR-221 and miR-222. Based on the enrichment of H3K4me3, which is at the TSS of ...

Non-protein-coding RNAs (ncRNAs) are increasingly being recognized as having important regulatory roles. Although much recent attention has focused on tiny 22- to 25-nucleotide microRNAs, several functional ncRNAs are orders of magnitude larger in size. Examples of such macro ncRNAs include Xist and Air, which in mouse are 18 and 108 kilobases (Kb), respectively. We surveyed the 102,801 FANTOM3 mouse cDNA clones and found that Air and Xist were present not as single, full-length transcripts but as a cluster of multiple, shorter cDNAs, which were unspliced, had little coding potential, and were most likely primed from internal adenine-rich regions within longer parental transcripts. We therefore conducted a genome-wide search for regional clusters of such cDNAs to find novel macro ncRNA candidates. Sixty-six regions were identified, each of which mapped outside known protein-coding loci and which had a mean length of 92 Kb. We detected several known long ncRNAs within these regions, supporting the basic

Non-protein-coding RNAs (ncRNAs) are increasingly being recognized as having important regulatory roles. Although much recent attention has focused on tiny 22- to 25-nucleotide microRNAs, several functional ncRNAs are orders of magnitude larger in size. Examples of such macro ncRNAs include Xist and Air, which in mouse are 18 and 108 kilobases (Kb), respectively. We surveyed the 102,801 FANTOM3 mouse cDNA clones and found that Air and Xist were present not as single, full-length transcripts but as a cluster of multiple, shorter cDNAs, which were unspliced, had little coding potential, and were most likely primed from internal adenine-rich regions within longer parental transcripts. We therefore conducted a genome-wide search for regional clusters of such cDNAs to find novel macro ncRNA candidates. Sixty-six regions were identified, each of which mapped outside known protein-coding loci and which had a mean length of 92 Kb. We detected several known long ncRNAs within these regions, supporting the basic

Several studies have demonstrated that LncRNAs can play major roles in cancer development. The creation of a catalog of LncRNAs expressed in T cell acute lymphoblastic leukemia (T-ALL) is thus of particular importance. However, this task is challenging as LncRNA expression is highly restricted in time and space manner and thus may greatly differ between samples. We performed a systematic transcript discovery in RNA-Seq data obtained from T-ALL primary cells and cell lines. This led to the identification of 2560 novel LncRNAs. After the integration of these transcripts into a large compendium of LncRNAs (n = 30478) containing both known LncRNAs and those previously described in T-ALLs, we then performed a systematic genomic and epigenetic characterization of these transcript models demonstrating that these novel LncRNAs share properties with known LncRNAs. Finally, we provide evidence that these novel transcripts could be enriched in LncRNAs with potential oncogenic effects and identified a subset of

Viruses regulate host metabolic networks to improve their survival. The molecules that are responsive to viral infection and regulate such metabolic changes are hardly known, but are essential for understanding viral infection. Here we identify a long noncoding RNA (lncRNA) that is induced by multiple viruses, but not by type I interferon (IFN-I), and facilitates viral replication in mouse and human cells. In vivo deficiency of lncRNA-ACOD1 (a lncRNA identified by its nearest coding gene Acod1, aconitate decarboxylase 1) significantly attenuates viral infection through IFN-I-IRF3 (interferon regulatory factor 3)-independent pathways. Cytoplasmic lncRNA-ACOD1 directly binds the metabolic enzyme glutamic-oxaloacetic transaminase (GOT2) near the substrate niche, enhancing its catalytic activity. Recombinant GOT2 protein and its metabolites could rescue viral replication upon lncRNA-ACOD1 deficiency and increase lethality. This work reveals a feedback mechanism of virus-induced lncRNA-mediated ...

Antisense RNA (asRNA), also referred as antisense transcript, natural antisense transcript (NAT) or antisense oligonucleotide, is a single stranded RNA that is complementary to a protein coding messenger RNA (mRNA) that hybridize with it and thereby blocks its translation into protein. asRNAs occur naturally in nature and have been found in both prokaryotes and eukaryotes and belongs to a subtype of long noncoding RNA (lncRNA) that is larger than 200 nucleotides. The primary function of asRNA is regulating gene expression. asRNAs may also be produced synthetically and have found wide spread use as research tools for gene knockdown. They may also have therapeutic applications. Some of the earliest asRNAs were discovered while investigating functional proteins. An example was micF asRNA. While characterizing the outer membrane porin ompC in E.coli, some of the ompC promoter clones observed were capable of repressing the expression of other membrane porin such as ompF. The region responsible for ...

TY - JOUR. T1 - Non-human lnc-DC orthologs encode wdnm1-like protein. AU - Dijkstra, Johannes M.. AU - Ballingall, Keith T.. N1 - Publisher Copyright: © 2014 Dijkstra JM and Ballingall KT.. PY - 2014/9/30. Y1 - 2014/9/30. N2 - In a recent publication in Science, Wang et al. found a long noncoding RNA (lncRNA) expressed in human dendritic cells (DC), which they designated lnc-DC. Based on lentivirus-mediated RNA interference (RNAi) experiments in human and murine systems, they concluded that lnc-DC is important in differentiation of monocytes into DC. However, Wang et al. did not mention that their so-called mouse lnc-DC ortholog? gene was already designated Wdnm1-like? and is known to encode a small secreted protein. We found that incapacitation of the Wdnm1-like open reading frame (ORF) is very rare among mammals, with all investigated primates except for hominids having an intact ORF. The null-hypothesis by Wang et al. therefore should have been that the human lnc-DC transcript might only ...

Long Noncoding RNA HULC Accelerates Liver Cancer by Inhibiting PTEN via Autophagy Cooperation to miR15a HULC accelerated malignant progression of liver cancer cells in vitro and in vivo. HULC inhibited PTEN through ubiquitin-proteasome system mediated by autophagy-P62. HULC increased the expression of P62 via decreasing mature miR15a. [Mol Cancer] Full Article Inflammasome Activation in Kupffer Cells Confers a Protective Response in Nonalcoholic Steatohepatitis through Pigment Epithelium-Derived Factor Expression Investigators identified pigment epithelium-derived factor, a secreted, moonlighting hepatokine as one hepatoprotective agent in mice with diet-induced nonalcoholic steatohepatitis. [FASEB J] Abstract TRIM52 Up-Regulation in Hepatocellular Carcinoma Cells Promotes Proliferation, Migration and Invasion through the Ubiquitination of PPM1A Tripartite motif containing 52 (TRIM52) was found interacted with Mg2+/Mn2+ dependent 1A (PPM1A) and TRIM52 down-regulation inhibited the ubiquitination ...

The majority of the human genome is transcribed into non-protein-coding RNA. Hence, RNA is also the primary product of the cancer genome. We have defined the ncRNA expression landscape of lung, breast and liver cancer providing a comprehensive expression map of over 17000 long ncRNAs and discovering new lncRNAs associated with cancer whose molecular and cellular functions we are currently elucidating exploiting our custom siRNA library targeting 638 tumor-associated lncRNAs. The nuclear lncRNA MALAT1 was one of the first lncRNAs associated with cancer: it is associated with metastasis development in lung cancer. However, its high abundance and nuclear localization have hampered its functional analysis. To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements site-specifically into the MALAT1 locus. This approach yielded a 1000-fold silencing of MALAT1 providing a unique loss-of-function model. ...

Long noncoding RNAs (lncRNAs) are a heterogenous group of RNAs, which can encode small proteins. The extent to which developmentally regulated lncRNAs are translated and whether the produced microproteins are relevant for human development is unknown. Using a human embryonic stem cell (hESC)-based pancreatic differentiation system, we show that many lncRNAs in direct vicinity of lineage-determining transcription factors (TFs) are dynamically regulated, predominantly cytosolic, and highly translated. We genetically ablated ten such lncRNAs, most of them translated, and found that nine are dispensable for pancreatic endocrine cell development. However, deletion of LINC00261 diminishes insulin+ cells, in a manner independent of the nearby TF FOXA2. One-by-one disruption of each of LINC00261s open reading frames suggests that the RNA, rather than the produced microproteins, is required for endocrine development. Our work highlights extensive translation of lncRNAs during hESC pancreatic ...

Clinical samples and study approval. A total of 266 pairs of tumor tissues and NATs from patients with BCa who underwent surgery was obtained at Sun Yat-sen Memorial Hospital (Cohort 1). Urine and blood samples were obtained from another 206 patients with BCa and 120 healthy participants (Cohort 2). In both cohorts, patients were eligible if they had pathologically confirmed BCa. The clinical features of the patients are summarized in Supplemental Table 1 and Supplemental Table 7. All experiments were conducted with the approval of the Committees for Ethical Review of Research involving Human Subjects at Sun Yat-sen University. Written informed consent was obtained from all participants prior to sample collection.. Cell lines and cell culture. The human BCa cell lines UM-UC-3 (CRL-1749), 5637 (HTB-9), and T24 (HTB-4), and the immortalized normal human urothelial cell line SV-HUC-1 (CRL-9520) were purchased from American Type Culture Collection. UM-UC-3 and T24 cells were cultured in DMEM (Gibco) ...