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CBX2通过YAP磷酸化调控肝癌细胞的增殖和凋亡

CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma.

作者信息

Mao Jiakai, Tian Yu, Wang Chengye, Jiang Keqiu, Li Rui, Yao Yifan, Zhang Rixin, Sun Deguang, Liang Rui, Gao Zhenming, Wang Qi, Wang Liming

机构信息

Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.

出版信息

J Cancer. 2019 Jun 2;10(12):2706-2719. doi: 10.7150/jca.31845. eCollection 2019.

Abstract

Chromobox 2 (CBX2), a chromobox family protein, is a crucial component of the polycomb group complex: polycomb repressive complex 1 (PRC1). Research on CBX2 as an oncogene has been published in recent years. However, the connection between CBX2 and hepatocellular carcinoma (HCC) has not been studied. In this article, based on the results of immunohistochemical (IHC) staining of HCC and adjacent liver tissue microarrays, we found that high CBX2 expression is associated with poor prognosis in HCC patients. The results of a CCK8 assay, a clonogenic survival assay and a nude mouse tumorigenicity assay showed that knockdown of CBX2 inhibited the proliferation of HCC cells. According to the results of Annexin V-FITC/propidium iodide (PI) staining-based fluorescence activated cell sorting (FACS) analysis, knockdown of CBX2 increased HCC cell apoptosis. Furthermore, the RNA-seq results revealed that knockdown of CBX2 inhibited the expression of WTIP, which is an inhibitor of the Hippo pathway. We used western blotting to validate the mechanism and discovered that knockdown of CBX2 increased the phosphorylation of YAP, which explains why knockdown of CBX2 inhibits proliferation and increases apoptosis in HCC cells. In conclusion, CBX2 could be a potential target for HCC anticancer treatment.

摘要

染色体盒蛋白2(CBX2)是一种染色体盒家族蛋白,是多梳蛋白复合体:多梳抑制复合体1(PRC1)的关键组成部分。近年来已有关于CBX2作为癌基因的研究发表。然而,CBX2与肝细胞癌(HCC)之间的联系尚未得到研究。在本文中,基于HCC及相邻肝组织微阵列的免疫组织化学(IHC)染色结果,我们发现CBX2高表达与HCC患者的不良预后相关。CCK8检测、克隆形成存活检测和裸鼠致瘤性检测结果表明,敲低CBX2可抑制HCC细胞的增殖。根据基于膜联蛋白V-异硫氰酸荧光素/碘化丙啶(PI)染色的荧光激活细胞分选(FACS)分析结果,敲低CBX2可增加HCC细胞凋亡。此外,RNA测序结果显示,敲低CBX2可抑制Hippo通路抑制剂WTIP的表达。我们使用蛋白质免疫印迹法验证了该机制,并发现敲低CBX2可增加YAP的磷酸化,这解释了敲低CBX2为何会抑制HCC细胞增殖并增加其凋亡。总之,CBX2可能是HCC抗癌治疗的一个潜在靶点。

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