RNF128 Promotes Malignant Behaviors Via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2020 Oct 29

PMID 33116595

Citations 10

Authors

Xue-Song Bai

Chi Zhang

Rui Peng

Guo-Qing Jiang

Sheng-Jie Jin

Qian Wang

Ai-Wu Ke

Dou-Sheng Bai

Affiliations

Soon will be listed here.

Abstract

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.

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