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

• Main Authors: Bai XS, Zhang C, Peng R, Jiang GQ, Jin SJ, Wang Q, Ke AW, Bai DS
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-10-01
• Series: OncoTargets and Therapy
• Subjects: hepatocellular carcinoma; rnf128; ubiquitination; egfr/mek/erk signaling pathway; prognosis
• Online Access: https://www.dovepress.com/rnf128-promotes-malignant-behaviors-via-egfrmekerk-pathway-in-hepatoce-peer-reviewed-article-OTT

Xue-Song Bai,1,* Chi Zhang,2,* Rui Peng,2,* Guo-Qing Jiang,2 Sheng-Jie Jin,2 Qian Wang,2 Ai-Wu Ke,3 Dou-Sheng Bai2 1The First Clinical Medical College, Dalian Medical University, Dalian, Liaoning 116044, People’s Republic of China; 2Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou 225009, Jiangsu, People’s Republic of China; 3Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dou-Sheng BaiClinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, Jiangsu 225000, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail]: 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