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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 .

circ LARP 4 induces cellular senescence through regulating miR‐761/ RUNX 3/p53/p21 signaling in hepatocellular carcinoma