Circ-RNF13, as an oncogene, regulates malignant progression of HBV-associated hepatocellular carcinoma cells and HBV infection through ceRNA pathway of circ-RNF13/miR-424-5p/TGIF2.
Circ-RNF13, as an oncogene, regulates malignant progression of HBV-associated hepatocellular carcinoma cells and HBV infection through ceRNA pathway of circ-RNF13/miR-424-5p/TGIF2.
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DOI：
10.17305/bjbms.2020.5266
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发表时间：
2021-10-01
影响因子：
3.4
通讯作者：
Wu X
中科院分区：
文献类型：
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作者：
Chen Y;Li S;Wei Y;Xu Z;Wu X
环状RNA RNF13(CIRC-RNF13；ID：HSA_CIRC_0067717)是新发现的在乙肝病毒相关性肝细胞癌患者中异常上调的基因。然而，其作用和机制仍有待进一步诠释。首先，应用实时定量聚合酶链式反应(RT-qPCR)检测了人肝细胞癌组织和表达乙肝病毒的细胞(Huh7-HBV和Hep3B-HBVc)中CIRC-RNF13的表达，并伴随着转化生长因子β诱导的同源异型盒2(TGIF2)的上调和microRNA(MiR)-424-5p的下调。采用MTS实验、集落形成实验、流式细胞术、酶联免疫吸附实验、Transwell实验和裸鼠移植瘤模型进行功能丧失实验。结果表明，封闭CIRC-RNF13可提高Huh7-HBV和Hep3B-HBV细胞的凋亡率，但在体外抑制细胞的增殖、集落形成、迁移和侵袭，抑制体内肿瘤生长。RT-qPCR结果显示，CIRC-RNF13基因敲除后，HBVDNA拷贝数和乙肝表面抗原(HBs)、e抗原(HBeAg)水平均显著降低。根据双荧光素酶报告基因分析，在机制上，CIRC-RNF13和TGIF2可以直接与miR-424-5p相互作用，表明CIRC-RNF13和TGIF2是miR-424-5p的竞争内源RNA(CeRNAs)。在功能上，过表达miR-424-5p模拟和沉默miR-424-5p可在体外抵消CIRC-RNF13缺失对表达乙肝病毒的肝癌细胞的影响；TGIF2恢复部分取消miR-424-5p上调的作用。综上所述，CIRC-RNF13可能通过海绵miR-424-5p调控TGIF2来抑制乙肝相关肝癌细胞的恶性进展和乙肝病毒感染，为研究乙肝相关肝癌的发生和治疗提供了新的视角。
Circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is newly identified to be abnormally upregulated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. First of all, real-time quantitative PCR (RT-qPCR) was utilized to examine RNA expression, and circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGFβ-induced factor homeobox 2 (TGIF2) upregulation and microRNA (miR)-424-5p downregulation. Loss-of-functional experiments were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model. As a result, blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells, but inhibited cell proliferation, colony formation, migration, and invasion in vitro, along with suppressed tumor growth in vivo. Besides, RT-qPCR data showed that HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 could directly interacting with miR-424-5p according to dual-luciferase reporter assay, suggesting that circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Functionally, overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells in vitro; TGIF2 restoration partially abrogated the role of miR-424-5p upregulation. In conclusion, circ-RNF13 might sponge miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.
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影响因子：
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作者：
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影响因子：
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