乙型肝炎病毒上调 microRNA-328-3p 通过下调 FOXO4 促进 THLE-2 细胞损伤。

Upregulation of microRNA-328-3p by hepatitis B virus contributes to THLE-2 cell injury by downregulating FOXO4.

机构信息

Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, No.87 Xiangya Road, Changsha, 410008, Hunan, China.

Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

J Transl Med. 2020 Mar 30;18(1):143. doi: 10.1186/s12967-020-02299-8.

BACKGROUND

Hepatitis B virus (HBV) remains a major cause of chronic hepatitis and hepatocellular carcinoma, and miRNAs play important roles in HBV pathogenesis. Our previous study has shown that miR-328-3p is upregulated in HBV-infected patients and serves as a potent predictor for the prognosis of HBV-related liver failure.

METHODS

Here, the role of miR-328-3p in modulating cell injury in HBV-infected liver cells THLE-2 was investigated in detail. MiR-328-3p expression was examined using qRT-PCR. The levels of pro-inflammatory cytokines were measured using ELISA. HBV RNA and HBV DNA levels were quantified. The interactions between STAT3 and miR-328-3p promoter as well as miR-328-3p and FOXO4 were analyzed using chromatin immunoprecipitation (CHIP) assay and luciferase reporter assay, respectively. THLE-2 cell injury was evaluated by examining cell viability and apoptosis.

RESULTS

HBV promoted expression of miR-328-3p through the STAT3 signal pathway and that increasingly expressed miR-328-3p downregulated its target FOXO4, leading to the promotion of cell injury in HBV-infected liver cells THLE-2.

CONCLUSION

These data demonstrate that HBV-STAT3-miR-328-3p-FOXO4 regulation pathway may play an important role in the pathogenesis of HBV infection.

背景

乙型肝炎病毒（HBV）仍然是慢性肝炎和肝细胞癌的主要原因，miRNAs 在 HBV 发病机制中发挥重要作用。我们之前的研究表明，miR-328-3p 在 HBV 感染患者中上调，并作为 HBV 相关肝衰竭预后的有力预测因子。

方法

本研究详细研究了 miR-328-3p 在调节 HBV 感染的 THLE-2 肝细胞细胞损伤中的作用。使用 qRT-PCR 检测 miR-328-3p 的表达。使用 ELISA 测量促炎细胞因子的水平。定量检测 HBV RNA 和 HBV DNA 水平。使用染色质免疫沉淀（CHIP）测定和荧光素酶报告基因测定分别分析 STAT3 与 miR-328-3p 启动子以及 miR-328-3p 和 FOXO4 之间的相互作用。通过检测细胞活力和细胞凋亡来评估 THLE-2 细胞损伤。