Journal ArticleDOI
A critical role for the long non‐coding RNA GAS5 in proliferation and apoptosis in non‐small‐cell lung cancer
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TLDR
Findings suggest that GAS5 is a tumor suppressor in NSCLC, and the action of GAS4 is mediated by p53‐dependent and p53-independent pathways, and may be a novel therapeutic target in patients with NSCLCs.Abstract:
In more recent years, long non-coding RNAs (lncRNAs) have been investigated as a new class of regulators of cellular processes, such as cell growth, apoptosis, and carcinogenesis. Although lncRNAs are dysregulated in numerous cancer types, limited data are available on the expression profile and functional role of lncRNAs in non-small cell lung cancer (NSCLC). In the present study, we determined the expression pattern of the growth arrest-specific transcript 5 (GAS5) in 72 NSCLC specimens by qRT-PCR and assess its biological functions in the development and progression of NSCLC. The results revealed that GAS5 expression was down-regulated in cancerous tissues compared to adjacent noncancerous tissues (P < 0.05) and was highly related to tumor size and TNM stage (P < 0.05). This correlation between GAS5 and clinicopathological parameters indicates that GAS5 might function as a tumor suppressor. Furthermore, GAS5 overexpression increased tumor cell growth arrest and induced apoptosis in vitro and in vivo. Meanwhile, siRNA-mediated knockdown of GAS5 promoted tumor cell growth. Importantly, through western blot analysis, we found that ectopic expression of GAS5 significantly up-regulated p53 expression and down-regulated transcription factor E2F1 expression. Taken together, these findings suggest that GAS5 is a tumor suppressor in NSCLC, and the action of GAS5 is mediated by p53-dependent and p53-independent pathways. GAS5 could serve as a potential diagnostic marker for NSCLC and may be a novel therapeutic target in patients with NSCLC.read more
Citations
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A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response
Maite Huarte,Mitchell Guttman,Mitchell Guttman,David M. Feldser,Manuel Garber,Magdalena J. Koziol,Magdalena J. Koziol,Daniela Kenzelmann-Broz,Ahmad M. Khalil,Ahmad M. Khalil,Or Zuk,Ido Amit,Michal Rabani,Laura D. Attardi,Aviv Regev,Aviv Regev,Eric S. Lander,Eric S. Lander,Eric S. Lander,Tyler Jacks,John L. Rinn,John L. Rinn +21 more
TL;DR: In this paper, the identification of lincRNAs (lincRNA-p21) that serve as a repressor in p53-dependent transcriptional responses was reported, and the observed transcriptional repression was mediated through the physical association with hnRNP-K at repressed genes and regulation of p53 mediates apoptosis.
BookDOI
Long Noncoding RNAs
TL;DR: The chapter shows that the current understanding of what is a gene should be revised, in order to clearly define the complex relationship between product-coding regions, regulatory sequences, and the organism’s phenotype.
Journal ArticleDOI
Apoptosis, autophagy, necroptosis, and cancer metastasis
TL;DR: This review summarizes the recent advances in the understanding of the mechanisms by which key regulators of apoptosis, autophagy, and necroptosis participate in cancer metastasis and discusses the crosstalk between apoptosis-autophagy-and-novoptosis involved in the regulation of cancer metastatic processes.
Journal ArticleDOI
Long non-coding RNAs and complex diseases: from experimental results to computational models
TL;DR: Some state-of-the-art computational models are introduced, which could be effectively used to identify disease-related lncRNAs on a large scale and select the most promising disease- related lnc RNAs for experimental validation and discussed the future directions of developing computational models for lncRNA research.
Journal ArticleDOI
Clinical utility of circulating non-coding RNAs — an update
TL;DR: A compendium of miRNAs and long ncRNAs that have been reported in the literature to be present in human body fluids and that have the potential to be used as diagnostic and prognostic cancer biomarkers is provided.
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