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染色体盒同源物8(CBX8)与Y盒结合蛋白1(YBX1)相互作用,以促进肝癌细胞的细胞增殖。

Chromobox homolog 8 (CBX8) Interacts with Y-Box binding protein 1 (YBX1) to promote cellular proliferation in hepatocellular carcinoma cells.

作者信息

Xiao Lushan, Zhou Zixiao, Li Wenwen, Peng Jie, Sun Qingcan, Zhu Hongbo, Song Yang, Hou Jin-Lin, Sun Jingyuan, Cao Hui-Chuan, Zhongyi Dong, Wu Dehua, Liu Li

机构信息

State Key Laboratory of Organ Failure Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.

Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, China.

出版信息

Aging (Albany NY). 2019 Sep 8;11(17):7123-7149. doi: 10.18632/aging.102241.

Abstract

Polycomb group (PcG) proteins have recently been identified as critical regulators in tumor initiation and development. However, the function of CBX8 in human hepatocellular carcinoma (HCC) remains largely unknown. Our study was designed to explore the biological function and clinical implication of CBX8 in HCC. We investigated the interplay between CBX8 and cell cycle through Gene Set Enrichment Analysis and western blotting. Bioinformatics tools and co-immunoprecipitation were used to explore cell cycle regulation. Finally, we studied the expression and clinical significance of CBX8 in HCC through 3 independent datasets. CBX8 was upregulated in HCC and its expression correlated with cell cycle progression. CyclinD1 was downregulated by CBX8 knockdown but upregulated by CBX8 overexpression. YBX1 interacted with CBX8 and regulated the cell cycle. Moreover, targeting YBX1 with specific siRNA impaired CBX8-mediated regulation of CyclinD1. CBX8 overexpression boosted HCC cell growth, while CBX8 knockdown suppressed cell proliferation. Further, YBX1 interacted with CBX8. YBX1 knockdown compromised the proliferation of CBX8 overexpressing cells. CBX8 promotes HCC cell proliferation through YBX1 mediated cell cycle progression and is related to poor HCC prognoses. Therefore, CBX8 may serve as a potential target for the diagnosis and treatment of HCC.

摘要

多梳蛋白家族(PcG)蛋白最近被确定为肿瘤发生和发展的关键调节因子。然而,CBX8在人类肝细胞癌(HCC)中的功能仍 largely未知。我们的研究旨在探讨CBX8在HCC中的生物学功能和临床意义。我们通过基因集富集分析和蛋白质印迹研究了CBX8与细胞周期之间的相互作用。使用生物信息学工具和免疫共沉淀来探索细胞周期调控。最后,我们通过3个独立数据集研究了CBX8在HCC中的表达及其临床意义。CBX8在HCC中上调,其表达与细胞周期进程相关。敲低CBX8可下调细胞周期蛋白D1(CyclinD1),而过表达CBX8则使其上调。YBX1与CBX8相互作用并调节细胞周期。此外,用特异性小干扰RNA(siRNA)靶向YBX1会损害CBX8介导的对CyclinD1的调控。过表达CBX8可促进HCC细胞生长,而敲低CBX8则抑制细胞增殖。此外,YBX1与CBX8相互作用。敲低YBX1会损害过表达CBX8的细胞的增殖。CBX8通过YBX1介导的细胞周期进程促进HCC细胞增殖,并且与HCC预后不良相关。因此,CBX8可能成为HCC诊断和治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e6a/6756871/8e6ae30db238/aging-11-102241-g001.jpg

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