RHNO1 disruption inhibits cell proliferation and induces mitochondrial apoptosis via PI3K/Akt pathway in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) represents one of the primary liver malignancies with poor prognosis. RHNO1, which implicated in the ATR-CHK1 signaling pathway thus functions in the DNA replication stress response. However, the role and molecular mechanisms of RHNO1 in HCC remain largely elusive. Here, we imply that RHNO1 is elevated in HCC tumor tissues and that high expression of RHNO1 predicts poor prognosis of HCC patients. Moreover, RHNO1 mRNA, especially protein levels were significantly increased in most HCC cells. Knockdown of RHNO1 through small interfering RNAs (siRNAs) inhibited the proliferation and triggered cell apoptosis of HCC cells both in vitro and in vivo. Specifically, we find that RHNO1 deficiency confers apoptosis via mitochondrial-mediated pathway. Mechanistically, silencing of RHNO1 impeded HCC proliferation and induced apoptosis by inactivating the PI3K/Akt pathway. Overall, these findings unravel that RHNO1 functions as an oncogene in HCC, and involved in regulating mitochondrial apoptosis to promote HCC thus may serve as a therapeutic and diagnostic target for HCC.