期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 38, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13046-019-1113-3
关键词
Hepatocellular carcinoma; RNF38; AHNAK; TGF- signaling; Prognosis
类别
资金
- National Natural Science Foundation of China [81302100, 81672825, 81472840, 81502526, 81871909, 81702861]
- Cancer Biology State Key Laboratory Project [CBSKL201717]
- Outstanding Clinical Discipline Project of Shanghai Pudong [PWYgy2018-02]
BackgroundRING finger protein 38 (RNF38), a member of the RNF protein family, has just emerged as a vital driver of cancer progression. However, the oncogenic mechanisms of RNF38 remain unexplored.MethodsUsing frozen tumor tissue and tissue microarray from hepatocellular carcinoma (HCC) patients, we tried to probe the expression of RNF38 in HCC and its clinical value. Then the biological functions of RNF38 were analyzed in vivo and vitro. Stable isotope labeling with amino acids (SILAC) in cell culture and co-immunoprecipitation proteomic analyses were combined to reveal the potential mechanism of RNF38 in HCC progression.ResultsWe report that RNF38 expression was markedly higher in HCC tissues than in peritumor tissues. Correspondingly, RNF38 overexpression promoted the HCC cell migration and invasion and inhibited apoptosis both in vitro and in vivo. And elevated RNF38 expression induced HCC cell epithelial-mesenchymal transition by facilitating transforming growth factor- (TGF-) signaling via ubiquitinating and degrading neuroblast differentiation-associated protein (AHNAK), a well-established inhibitor of TGF- signaling. Furthermore, AHNAK interference restored the HCC cell invasion and metastasis deprived by RNF38 downregulation. Clinically, elevated RNF38 and transforming growth factor beta receptor 1 (TGFBR1) expression was related to short overall survival (OS) and high cumulative recurrence rates in HCC patients.ConclusionsHigh levels of RNF38 promote HCC by facilitating TGF- signaling and are a novel marker for predicting the prognosis of HCC patients and a potential therapeutic target in HCC.
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