Recently, more than 1000 large intergenic noncoding RNAs (lincRNAs) have been reported. These RNAs are evolutionarily conserved in mammalian genomes and thus presumably function in diverse biological processes. Here, we report the identification of lincRNAs that are regulated by p53. One of these lincRNAs (lincRNA-p21) serves as a repressor in p53-dependent transcriptional responses. Inhibition of lincRNA-p21 affects the expression of hundreds of gene targets enriched for genes normally repressed by p53. The observed transcriptional repression by lincRNA-p21 is mediated through the physical association with hnRNP-K. This interaction is required for proper genomic localization of hnRNP-K at repressed genes and regulation of p53 mediates apoptosis. We propose a model whereby transcription factors activate lincRNAs that serve as key repressors by physically associating with repressive complexes and modulate their localization to sets of previously active genes.

A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response

https://www.gastrojournal.org/article/S0016-5085(15)01005-7/pdf

Epigenetic Alterations in Colorectal Cancer: Emerging Biomarkers

Background Oesophageal cancer is one of the most deadly forms of cancer worldwide. Long non-coding RNAs (lncRNAs) are often found to have important regulatory roles. Objective To assess the lncRNA expression profile of oesophageal squamous cell carcinoma (OSCC) and identify prognosis-related lncRNAs. Method LncRNA expression profiles were studied by microarray in paired tumour and normal tissues from 119 patients with OSCC and validated by qRT-PCR. The 119 patients were divided randomly into training (n=60) and test (n=59) groups. A prognostic signature was developed from the training group using a random Forest supervised classification algorithm and a nearest shrunken centroid algorithm, then validated in a test group and further, in an independent cohort (n=60). The independence of the signature in survival prediction was evaluated by multivariable Cox regression analysis. Results LncRNAs showed significantly altered expression in OSCC tissues. From the training group, we identified a three-lncRNA signature (including the lncRNAs ENST00000435885.1, XLOC_013014 and ENST00000547963.1) which classified the patients into two groups with significantly different overall survival (median survival 19.2 months vs >60 months, p 60 months, p=0.0030) and independent cohort (median survival 25.8 months vs >48 months, p=0.0187) and showed similar prognostic values in both. Multivariable Cox regression analysis showed that the signature was an independent prognostic factor for patients with OSCC. Stratified analysis suggested that the signature was prognostic within clinical stages. Conclusions Our results suggest that the three-lncRNA signature is a new biomarker for the prognosis of patients with OSCC, enabling more accurate prediction of survival.

https://gut.bmj.com/content/gutjnl/63/11/1700.full.pdf

LncRNA profile study reveals a three-lncRNA signature associated with the survival of patients with oesophageal squamous cell carcinoma

Transcription of a large part of the human genome results in RNA transcripts that have limited or no protein-coding potential. These include long noncoding RNAs (lncRNAs), which are defined as being ≥200 nucleotides long. Unlike microRNAs, which have been extensively studied, little is known about the functional role of lncRNAs. However, studies over the past 5 years have shown that lncRNAs interfere with tissue homeostasis and have a role in pathological processes, including in the kidney and heart. The developmental expression of the microRNA sponge H19, for example, is altered in the kidneys of embryos carried by hyperglycaemic mothers, and the lncRNA Malat1 regulates hyperglycaemia-induced inflammation in endothelial cells. Putative roles for other lncRNAs have been identified in conditions such as heart failure, cardiac autophagy, hypertension, acute kidney injury, glomerular diseases, acute allograft rejection and renal cell carcinoma. This Review outlines our current understanding of the role and function of lncRNAs in kidney and cardiovascular disease as novel important regulators and potential therapeutic entry points of disease progression.

Long noncoding RNAs in kidney and cardiovascular diseases

ADAR1 Activation Drives Leukemia Stem Cell Self-Renewal by Impairing Let-7 Biogenesis

Background
Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of cancers. In this study, we described lncRNAs profiles in 6 pairs of human renal clear cell carcinoma (RCCC) and the corresponding adjacent nontumorous tissues (NT) by microarray.

/pdf/lncrnas-expression-signatures-of-renal-clear-cell-carcinoma-4fy4puq5gh.pdf

LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray.

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LncRNAs expression signatures of renal clear cell carcinoma revealed by microarray.