Circ_0007841通过miR-338-3p靶向JAG1促进肝癌细胞恶性生物学活性的机制研究

doi:10.3969/j.issn.1006-6233.2023.11.07

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摘要 目的: 探究肝癌恶性生物学活性的调控机制。方法: 购买人源正常肝上皮细胞THLE-3与肝癌细胞系BEL-7405、SNU-387、MHCC-97H、HCCLM3、Huh7,转染si-0007841/NC或miR-338-3p inhibitor/NC至Huh7细胞,qRT-PCR检测circ_0007841、miR-338-3p、JAG1的表达。在各组Huh7中利用CCK-8、Transwell检测各组的增殖活力、迁移、侵袭能力变化。Circular RNA Interactome、miRWalk预测circ_0007841与miR-338-3p、miR-338-3p与JAG1的靶向关系,双荧光素酶报告实验验证靶向结合。结果: circ_0007841在HCC中呈高表达,抑制circ_0007841的表达可以抑制HCC的增殖活力与迁移、侵袭能力;进一步抑制miR-338-3p的表达后,可以部分逆转低表达circ_0007841对HCC恶性行为的遏制。在HCC中,circ_0007841可以靶向抑制miR-338-3p的表达,而miR-338-3p则可以靶向抑制JAG1的表达。结论: 肝癌中高表达的circ_0007841通过竞争性结合miR-338-3p增加JAG1转录,最终促进肝癌细胞恶性生物学活性。

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关键词 ：肝癌, circ_0007841, miR-338-3p, JAG1, 增殖活力, 迁移, 侵袭

Abstract：Objective: To explore the regulatory mechanism underlying the malignant biological activity of hepatocellular carcinoma (HCC). Methods: Human-derived normal hepatic epithelial cells THLE-3 and HCC cell lines,including BEL-7405,SNU-387,MHCC-97H,HCCLM3,and Huh7,were used.Huh7 cells were transfected with si-0007841/NC or miR-338-3p inhibitor/NC.Expression levels of circ_0007841,miR-338-3p,and JAG1 were analyzed using qRT-PCR.Proliferation viability,migration,and invasion ability were assessed using CCK-8 and transwell assays.Predictions of the targeting relationships between circ_0007841 and miR-338-3p,as well as miR-338-3p and JAG1,were performed using Circular RNA Interactome and miRWalk datasets.Dual luciferase reporter assays confirmed the target binding. Results: Circ_0007841 was found to be highly expressed in HCC.Inhibiting circ_0007841 expression led to a decrease in proliferation viability and a reduction in migration and invasion abilities of HCC.Further inhibition of miR-338-3p expression partially reversed the inhibitory effects on malignant behavior by low expression of circ_0007841.In HCC,circ_0007841 could target and inhibit the expression of miR-338-3p,while miR-338-3p could target and inhibit the expression of JAG1. Conclusion: High expression of circ_0007841 in hepatocellular carcinoma enhances JAG1 transcription by competitively binding with miR-338-3p,ultimately promoting malignant biological activities in HCC cells.

Key words： Hepatocellular carcinoma Circ_0007841 miR-338-3p JAG1 Proliferation viability Migration Invasion

基金资助:河北省2020年度医学科研课题计划,(编号:20200158)

通讯作者: 郑运周

引用本文:

龚一林, 郑运周, 赵艳微, 张洪雨, 黄涛. Circ_0007841通过miR-338-3p靶向JAG1促进肝癌细胞恶性生物学活性的机制研究[J]. 河北医学, 2023, 29(11): 1795-1800.
GONG Yilin, ZHENG Yunzhou, ZHAO Yanwei, et al. Mechanistic Study on the Regulation of Malignant Biological Activity of JAG1 Pathway in Hepatocellular Carcinoma Cells through miR-338-3p by Circ_0007841. HeBei Med, 2023, 29(11): 1795-1800.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.11.07 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I11/1795

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