PDCD6 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the AKT/GSK3β/β-catenin Pathway

作     者：WEN Shi Yuan LIU Yan Tong WEI Bing Yan MA Jie Qiong CHEN Yan Yan WEN Shi Yuan;LIU Yan Tong;WEI Bing Yan;MA Jie Qiong;CHEN Yan Yan

作者机构：College of Basic Medical SciencesShanxi Medical UniversityTaiyuan 030000ShanxiChina School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China Shanxi Key Laboratory of Experimental Animals and Animal Models for Human DiseasesLaboratory Animal CenterShanxi Medical UniversityTaiyuan 030000ShanxiChina School of MedicineJiangsu UniversityZhenjiang 212001JiangsuChina 

出 版 物：《Biomedical and Environmental Sciences》 (生物医学与环境科学（英文版）)

年 卷 期：2023年第36卷第3期

页      面：241-252页

核心收录：

学科分类：0830[工学-环境科学与工程（可授工学、理学、农学学位）] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by Shanxi Province Science Foundation for Youths Science Research Start-up Fund for Doctor of Shanxi Province [SD2115] Science Research Start-up Fund for Doctor of Shanxi Medical University [XD2021] Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi[2021L215]。 

主　　题：PDCD6 Hepatocellular carcinoma Proliferation Metastasis 

摘      要：Objective Programmed cell death 6(PDCD6), a Ca~(2+)-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas(HCCs).Methods The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium(MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6.Results The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis.Conclusion PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression.