Background: The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC.
Materials and Methods: Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC. Western blot and quantitative realtime polymerase chain reaction (qRT-PCR) were performed to examine expression levels of RNF128 in HCC tissues and cell lines. Effects of RNF128 on HCC cellular biological functions and the potential mechanism were evaluated through knockdown and overexpression assays in vitro and in vivo methods.
Results: RNF128 expression was found to be remarkably elevated in HCC tissues compared with adjacent normal tissues. Furthermore, the overexpression of RNF128 enhanced hepatoma cells proliferation, colony formation, migration, invasion, and apoptotic resistance both in vitro and in vivo. Mechanistically, RNF128 activated EGFR/MEK/ERK signaling pathway and the EGFR inhibitor, gefitinib partially reversed RNF128-enhanced proliferation, invasion, and migration in hepatoma cells.
Conclusion: RNF128 promotes HCC progression by activating EGFR/MEK/ERK signaling pathway, which might function as a novel prognostic molecular signature with the potential to be a candidate therapeutic target for HCC patients.
Keywords: hepatocellular carcinoma, RNF128, ubiquitination, EGFR/MEK/ERK signaling pathway, prognosis