Open Accesscirc LARP 4 induces cellular senescence through regulating miR‐761/ RUNX 3/p53/p21 signaling in hepatocellular carcinoma
Author(s) -
Chen Zhiqiang,
Zuo Xueliang,
Pu Liyong,
Zhang Yao,
Han Guoyong,
Zhang Long,
Wu Jindao,
Wang Xuehao
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13901
Subject(s) - senescence , cancer research , cell growth , biology , hepatocellular carcinoma , cell cycle , cell cycle checkpoint , cell , phenotype , signal transduction , downregulation and upregulation , microbiology and biotechnology , gene , genetics
Circular RNA s (circ RNA s), a novel class of non‐coding RNA s, have emerged as indispensable modulators in human malignancies. Aberrant cellular senescence is a phenotype observed in various cancers. The association of circ RNA s with cellular senescence in tumors is yet to determined. Here, we investigated the role of circ LARP 4 in cellular senescence and cell proliferation in hepatocellular carcinoma ( HCC ). Downregulated circ LARP 4 level was observed in HCC tissues and cell lines. Low expression level of circ LARP 4 independently predicted poor survival outcome. Gain‐of‐function and loss‐of‐function assays demonstrated that circ LARP 4 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 circ LARP 4‐overexpressed HCC cells and decreased in circ LARP 4‐silenced HCC cells. In vivo experiments further confirmed the tumor‐suppressing activity of circ LARP 4. Further mechanistic studies showed that circ LARP 4 dampened HCC progression by sponging miR‐761, thereby promoting the expression level of RUNX 3 and activating the downstream p53/p21 signaling. Our study revealed the role of circ LARP 4/miR‐761/ RUNX 3/p53/p21 signaling in HCC progression, providing a potential survival predictor and therapeutic candidate for HCC .