C-terminal-truncated hepatitis B virus X protein promotes hepatocarcinogenesis by activating the MAPK pathway,Microbial Pathogenesis

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C-terminal-truncated hepatitis B virus X protein promotes hepatocarcinogenesis by activating the MAPK pathway
Microbial Pathogenesis ( IF 3.8 ) Pub Date : 2021-08-12 , DOI: 10.1016/j.micpath.2021.105136
Chaojun Zhang ₁ , Chanchan Xiao ₁ , Guanhua Ren ₁ , Dongmei Cai ₁ , Long Long ₁ , Jilin Li ₁ , Kezhi Li ₁ , Yanping Tang ₁ , Tianren Huang ₁ , Wei Deng ₁

Affiliation

Purpose

C-terminally truncated hepatitis B virus X (ctHBx) is frequently detected in hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) integrated into their genomes, but the molecular mechanisms of ctHBx-related oncogenic signaling remain unclear. In this study, the effects of ctHBx on HepG2 cells were investigated by measuring ctHBx-induced changes in the cell cycle-related target proteins cell division cycle 25C (cdc25C) and p53 downstream of the mitogen-activated protein kinase (MAPK) pathway.

Materials and methods

ctHBx lentiviruses were constructed and transfected into HepG2 cells. Then, we investigated HepG2 cell line function by conducting the Cell Counting Kit-8 (CCK8) assay, clone formation assay, scratch wound testing, Transwell assays and flow cytometry to examine cell cycle and apoptosis. Western blotting (WB) was performed to detect proteins related to and downstream of the extracellular signal-regulated kinase(ERK)/c-Jun N-terminal kinase(JNK)/p38 MAPK pathway, including cdc25C and p53.

Results

ctHBx significantly enhanced the proliferation, migration, invasion and colony-forming capability of HepG2 cells. In addition, ctHBx activated the ERK/JNK/p38 MAPK signaling pathway to regulate cell viability by affecting the expression of cyclin-related proteins, including cdc25C and p53.

Conclusion

The present study demonstrates that ctHBx promote the formation and development of HCC via regulating MAPK/cdc25C and p53 axis. ctHBx should be the driving factor of HBV-induced hepatocarcinogenesis.

中文翻译：

C末端截短的乙型肝炎病毒X蛋白通过激活MAPK通路促进肝癌发生

目的

C 末端截短的乙型肝炎病毒 X (ctHBx) 在乙型肝炎病毒 (HBV) 整合到其基因组中的肝细胞癌 (HCC) 患者中经常检测到，但 ctHBx 相关致癌信号传导的分子机制仍不清楚。在本研究中，通过测量 ctHBx 诱导的细胞周期相关靶蛋白细胞分裂周期 25C (cdc25C) 和丝裂原活化蛋白激酶 (MAPK) 通路下游 p53 的变化来研究 ctHBx 对 HepG2 细胞的影响。

材料和方法

构建ctHBx慢病毒并将其转染到HepG2细胞中。然后，我们通过细胞计数试剂盒 8 (CCK8) 测定、克隆形成测定、划痕测试、Transwell 测定和流式细胞术来研究 HepG2 细胞系功能，以检查细胞周期和细胞凋亡。进行蛋白质印迹 (WB) 以检测与细胞外信号调节激酶 (ERK)/c-Jun N-末端激酶 (JNK)/p38 MAPK 通路相关和下游的蛋白质，包括 cdc25C 和 p53。