HBV upregulates AP-1 complex subunit mu-1 expression via the JNK pathway to promote proliferation of liver cancer cells
HBV upregulates AP-1 complex subunit mu-1 expression via the JNK pathway to promote proliferation of liver cancer cells
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HBV通过JNK途径上调AP-1复合体亚基mu-1表达促进肝癌细胞增殖
DOI：
10.3892/ol.2019.10291
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发表时间：
2019-07-01
期刊：
影响因子：
2.9
通讯作者：
Tang, Renxian
中科院分区：
文献类型：
--
作者：
Kou, Yanbo;Yan, Xiaoqing;Tang, Renxian
虽然B型肝炎病毒（HBV）感染是肝癌的原因，但其确切的作用机制仍不清楚。μ 1衔接蛋白是网格蛋白衔接子AP-1复合物的固有部分。除了其典型的生物学功能，涉及货物分选和囊泡运输，最近的研究表明，mu 1适应蛋白参与细胞生长和增殖。本研究的目的是研究网格蛋白接头AP-1复合物亚基mu-1（AP 1 M1）对肝癌细胞增殖的影响。本研究首次报道AP 1 M1在HBV转染的HepG2.215肝癌细胞中上调。AP 1 M1在HepG2.215细胞中的沉默抑制其增殖，而AP 1 M1在HepG 2细胞中的过表达促进细胞增殖。这些数据表明，AP 1 M1是参与HBV感染引起的肝癌进展的关键因素之一。此外，已证明HBV以JNK依赖性方式促进AP 1 M1表达。AP 1 M1表达水平的增加增强了蛋白激酶B的磷酸化，促进了细胞增殖。阐明AP 1 M1对肝癌细胞增殖的影响及其转录调控机制可能为HBV阳性肝癌的治疗提供新的靶点。
Although hepatitis B virus (HBV) infection is responsible for liver cancer, the exact mechanism of its action remains unclear. mu 1 adaptin is an intrinsic part of the clathrin adaptor AP-1 complex. In addition to its canonical biological function that involves cargo sorting and vesicular transport, recent studies have demonstrated that mu 1 adaptin participates in cell growth and proliferation. The aim of the present study was to investigate the effects of the clathrin adaptor AP-1 complex subunit mu-1 (AP1M1) on liver cancer cell proliferation. The present study reports for the first time that AP1M1 is upregulated in the HBV-transfected HepG2.215 liver cancer cells. Silencing of AP1M1 in HepG2.215 cells suppressed their proliferation, while the overexpression of AP1M1 in HepG2 cells promoted cell proliferation. The data suggested that AP1M1 is one of the crucial factors involved in the progression of liver cancer caused by HBV infection. In addition, it was demonstrated that HBV facilitated AP1M1 expression in a JNK-dependent manner. The increased expression levels of AP1M1 enhanced phosphorylation of protein kinase B and accelerated cell proliferation. Unraveling the effects of AP1M1 on liver cancer cell proliferation and the mechanism of AP1M1 transcriptional regulation may provide new therapeutic targets for HBV-positive liver cancer.