%0 Journal Article
%T circLARP4 induces cellular senescence through regulating miRİ\761/RUNX3/p53/p21 signaling in hepatocellular carcinoma
%A Guoyong Han
%A Jindao Wu
%A Liyong Pu
%A Long Zhang
%A Xuehao Wang
%A Xueliang Zuo
%A Yao Zhang
%A Zhiqiang Chen
%J Archive of "Cancer Science".
%D 2019
%R 10.1111/cas.13901
%X Circular RNAs (circRNAs), a novel class of nonİ\coding RNAs, have emerged as indispensable modulators in human malignancies. Aberrant cellular senescence is a phenotype observed in various cancers. The association of circRNAs with cellular senescence in tumors is yet to determined. Here, we investigated the role of circLARP4 in cellular senescence and cell proliferation in hepatocellular carcinoma (HCC). Downregulated circLARP4 level was observed in HCC tissues and cell lines. Low expression level of circLARP4 independently predicted poor survival outcome. Gainİ\ofİ\function and lossİ\ofİ\function assays demonstrated that circLARP4 suppressed HCC cell proliferation, mediated cell cycle arrest and induced senescence in vitro. Levels of p53 and p21, 2 key regulatory molecules in cellular senescence, were increased in circLARP4İ\overexpressed HCC cells and decreased in circLARP4İ\silenced HCC cells. In vivo experiments further confirmed the tumorİ\suppressing activity of circLARP4. Further mechanistic studies showed that circLARP4 dampened HCC progression by sponging miRİ\761, thereby promoting the expression level of RUNX3 and activating the downstream p53/p21 signaling. Our study revealed the role of circLARP4/miRİ\761/RUNX3/p53/p21 signaling in HCC progression, providing a potential survival predictor and therapeutic candidate for HCC
%K circLARP4
%K hepatocellular carcinoma
%K microRNA
%K RUNX3
%K senescence
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361555/