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2024, 06, v.40 1290-1296
乙型肝炎病毒通过miR-183-5p/THBS1轴促进肝癌细胞的增殖、迁移和侵袭
基金项目(Foundation):
邮箱(Email): 15710852742@sina.cn;
DOI: 10.13242/j.cnki.bingduxuebao.004614
摘要:

乙型肝炎病毒(Hepatitis B virus,HBV)是一种嗜肝性非细胞病变DNA病毒,可导致肝硬化、肝细胞癌(Hepatocellular carcinoma,HCC)等严重的肝脏疾病。目前认为HBV诱导的HCC涉及病毒因素和多个宿主因素之间复杂的相互作用。环状RNA(circRNA)是一种新型非编码RNA分子,在肿瘤的发生、发展中有重要的调控作用。有研究表明circRNA THBS1通过吸附miR-129-5p调控基因SOX4的表达促进非小细胞肺癌细胞的迁移和侵袭。然而,circRNA THBS1在肝癌中的作用机制尚不清楚。miRNA在多种癌症中作为致癌物或抑癌因子调控肿瘤的形成。本研究拟探究HBV对肝癌细胞的增殖、迁移和侵袭的影响和具体作用机制,CCK8和Transwell实验探究HBV对HepG2细胞增殖、迁移和侵袭的影响;双荧光素酶报告验证miR-183-5p和THBS1的关系;qRT-PCR检测miR-183-5p和THBS1 mRNA水平;Western blot检测增殖、迁移相关蛋白PCNA、MMP2和MMP9水平。在本研究中,用含HBV基因组的腺病毒感染HepG2细胞记为HBV组,正常HepG2细胞记为NC组。将过表达miR-183-5p、过表达miR-183-5p+沉默THBS1病毒载体转染至HBV感染的HepG细胞中,记为miR-183-5p过表达组、miR-183-5p+THBS1沉默组。与NC组相比,HBV组内miR-183-5p表达水平降低,THBS1表达水平升高,HepG2细胞增殖、迁移和侵袭能力显著增强;与HBV组相比,miR-183-5p过表达组、miR-183-5p+THBS1沉默组HepG2细胞增殖、迁移和侵袭能力被显著抑制。乙型肝炎病毒通过降低miR-183-5p表达上调THBS1,进而促进肝癌细胞的增殖、迁移和侵袭。

Abstract:

Hepatitis B virus(HBV) is a hepatotropic, non-cytopathogenic DNA virus that can cause severe liver diseases such as cirrhosis and hepatocellular carcinoma(HCC). It is widely accepted that HBV-induced HCC results from complex interactions between viral factors and multiple host factors. Circular RNA(circRNA) is a novel class of non-coding RNA molecules that play critical regulatory roles in tumorigenesis and cancer progression. Previous studies have shown that circRNA THBS1 promotes the migration and invasion of non-small cell lung cancer cells by adsorbing miR-129-5p and regulating the expression of the gene SOX4. However, the role of circRNA THBS1 in liver cancer remains unclear. miRNAs act as oncogenes or tumor suppressors in various cancers, regulating tumor formation. This study aims to explore the effects of HBV on the proliferation, migration, and invasion of liver cancer cells and elucidate the underlying mechanisms. CCK8 and Transwell assays were performed to investigate the effects of HBV on the proliferation, migration, and invasion of HepG2cells. The dual-luciferase reporter assay was used to confirm the interaction between miR-183-5p and THBS1.qRT-PCR was used to measure the expression levels of miR-183-5p and THBS1 mRNA, while Western blotting was employed to assess the levels of proliferation-and migration-related proteins, including PCNA, MMP2, and MMP9. In this study, HepG2 cells infected with an adenovirus containing the HBV genome were designated as the HBV group, and normal HepG2 cells were designated as the NC group. The overexpression of miR-183-5p or the combined overexpression of miR-183-5p and silencing of THBS1 was achieved via viral vector transfection into HBV-infected HepG2 cells, referred to as the miR-183-5p overexpression group and the miR-183-5p+THBS1 silenced group, respectively. Compared with the NC group, the expression of miR-183-5p was significantly downregulated, and the expression of THBS1 was upregulated in the HBV group, leading to enhanced proliferation, migration, and invasion of HepG2 cells. In contrast, compared with the HBV group, the proliferation, migration, and invasion of HepG2 cells were significantly inhibited in both the miR-183-5p overexpression group and the miR-183-5p+THBS1 silenced group. These findings suggest that HBV promotes the proliferation, migration, and invasion of liver cancer cells by downregulating miR-183-5p expression and upregulating THBS1.

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基本信息:

DOI:10.13242/j.cnki.bingduxuebao.004614

中图分类号:R512.62;R735.7

引用信息:

[1]吴耿刚,姚叶萍,姚金科等.乙型肝炎病毒通过miR-183-5p/THBS1轴促进肝癌细胞的增殖、迁移和侵袭[J].病毒学报,2024,40(06):1290-1296.DOI:10.13242/j.cnki.bingduxuebao.004614.

基金信息:

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