PES1 enhances proliferation and tumorigenesis in hepatocellular carcinoma via the PI3K/AKT pathway

Aim: We investigated the potential role of pescadillo ribosomal biogenesis factor 1 (PES1) in the development of hepatocellular carcinoma (HCC).

Material and methods: One hundred and thirty-four patients with hepatocellular carcinoma were chosen to evaluate the association between the expression of PES1 and survival, clinical characteristics of these patients. Western blotting, real-time PCR, immunohistochemistry, CCK-8 assay, colony formation and subcutaneous tumors in nude mice were conducted.

Key findings: We found that PES1 was commonly upregulated in HCC tissues and cells. Immunohistochemical analysis of 134 paraffin-embedded archived HCC tissues showed that the protein expression level of PES1 was positively correlated with clinical characteristics and reduced the survival time of HCC patients. Univariate and multivariate analysis revealed that PES1 expression may be an independent prognostic indicator of poorer overall survival in HCC patients. Furthermore, silencing of endogenous PES1 significantly inhibited the proliferation and tumorigenicity of SMMC 7721 and HepG2 cells in vitro as well as in vivo in nude mice. Finally, we found that PES1 affected cell proliferation by regulating the PI3K/AKT/GSK3β/cyclinD1 signaling pathway.

Significance: Our data suggest that PES1 may promote proliferation and tumorigenicity, and potentially representing a novel prognostic marker for overall survival in HCC.

Core tip: We report that pescadillo ribosomal biogenesis factor 1 (PES1) plays an oncogenic role in hepatocellular carcinoma, which was commonly upregulated in hepatocellular carcinoma tissues and cells. Immunostaining analysis found that the protein expression level of PES1 was positively correlated with clinical characteristics and reduced survival time of hepatocellular carcinoma patients. Multivariate analysis revealed that PES1 expression might be an independent prognostic indicator of survival in hepatocellular carcinoma patients. Furthermore, PES1 knockdown inhibited the proliferation and tumorigenesis in hepatocellular carcinoma cell lines. Additionally, we found that PES1 is involved in the cell proliferation by regulating the AKT/GSK3β/cyclinD1 signaling pathway.