CPEB1 Mediates Hepatocellular Carcinoma Cancer Stemness and Chemoresistance

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2018 Sep 22

PMID 30237545

Citations 24

Authors

Min Xu

Shiji Fang

Jingjing Song

Minjiang Chen

Qianqian Zhang

Qiaoyou Weng

Xiaoxi Fan

Weiqian Chen

Xulu Wu

Fazong Wu

Jianfei Tu

Zhongwei Zhao

Jiansong Ji

Affiliations

Soon will be listed here.

Abstract

Cancer stem cells (CSCs) are a subpopulation of cells within tumors that are believed to possess pluripotent properties and thought to be responsible for tumor initiation, progression, relapse and metastasis. Cytoplasmic polyadenylation element-binding protein 1 (CPEB1), a sequence-specific RNA-binding protein that regulates mRNA polyadenylation and translation, has been linked to cancer progression and metastasis. However, the involvement of CPEB1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we have demonstrated that CPEB1 directly regulates sirtuin 1 (SIRT1) mRNA to mediate cancer stemness in HCC. Cancer stemness was analyzed by self-renewal ability, chemoresistance, metastasis, expression of stemness-related genes and CSC marker-positive cell populations. The results indicate that CPEB1 is downregulated in HCC. Overexpression of CPEB1 dramatically reduced HCC cell stemness, whereas silencing CPEB1 enhances it. Using site-directed mutagenesis, a luciferase reporter assay, and immunoprecipitation, we found that CPEB1 could directly target the 3'-UTR of SIRT1, control poly(A) tail length and suppress its translation to mediate cancer stemness in vitro and in vivo. Overall, our findings suggest that the negative regulation between CPEB1 and SIRT1 contributes to the suppression of cancer stemness in HCC. CPEB1 may have potential as a therapeutic target in HCC.

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