医学分子生物学杂志 ›› 2022, Vol. 19 ›› Issue (2): 127-133.doi: 10.3870/j.issn.1672-8009.2022.02.006

• 论著 • 上一篇    下一篇

miR-188-3p 靶向 YAP1 抑制肝细胞癌的侵袭和迁移 

  

  1. 武汉大学中南医院1肝胆胰外科, 2超声影像科 武汉市, 430071
  • 出版日期:2022-03-31 发布日期:2022-04-18

miR-188-3p Inhibits the Invasion and Migration of Hepatocellular Carcinoma Cells by Targeting YAP1 

  1. 1Department of Hepatobiliary and Pancreatic Surgery, 2 Department of Ultrasonography, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
  • Online:2022-03-31 Published:2022-04-18

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摘要： 目的 探究 miR-188-3p 在肝细胞癌 (hepatocellular carcinoma, HCC) 中的表达及其抑制 HCC 细 胞侵袭和迁移的分子机制。 方法 利用 RT-qPCR 检测 miR-188-3p 在人 HCC 组织和细胞系中的表达情况, 进一步分析 miR-188-3p 表达在 HCC 中的临床价值; 利用 Western 印迹检测转染 miR-188-3p mimics 和 inhibitor 对 HCC 细胞中 YAP1 蛋白的影响; 分别利用 Transwell 侵袭和迁移实验检测各组细胞的侵袭和迁移能力; 利用双荧光素酶基因报告实验检测 miR-188-3p 对 YAP1 的靶向调控机制; 最后, 通过共转染 miR-188-3p mimics 和 YAP1 过表达质粒进行回复实验。 结果 miR-188-3p 在 HCC 组织中表达显著低于正常肝组织, 其 低表达与肿瘤大小、 肿瘤分化程度、 以及 TNM 分期密切相关 (P均 < 0. 05); 生存分析显示 HCC 组织中 miR-188-3p 低表达提示不良预后 (Log-rankP = 0. 025)。 体外细胞实验显示, 过表达 miR-188-3p 显著抑制 HCC 细胞的侵袭和迁移能力, 而抑制 miR-188-3p 表达则呈现出相反的效果。 双荧光素酶报告基因实验显 示, miR-188-3p 可通过与 YAP1 的 3′UTR 结合靶向抑制 YAP1 蛋白的表达。 回复实验结果证实, miR-188-3p 对 HCC 侵袭和迁移能力的抑制是通过抑制 YAP1 蛋白的表达实现。 结论 miR-188-3p 在 HCC 中呈低表达, 其通过靶向抑制 YAP1 的表达抑制 HCC 细胞的侵袭和迁移, 从而参与 HCC 的发生和进展。

关键词: 肝细胞癌, miR-188-3p, YAP1, 侵袭, 迁移

Abstract: Objective To explore the expression of miR-188-3p in hepatocellular carcinoma (HCC ) and its molecular mechanism of inhibiting the invasion and migration of HCC cells. Methods The expression of miR-188-3p in human HCC tissues and cell lines was detected by RT-qPCR, and the clinical value of miR-188-3p expression in HCC was further analyzed. Western blotting was used to detect the effects of transfection of the miR-188-3p mimics and inhibitor on YAP1 protein in HCC cells. Transwell invasion and migration assay were used to measure the invasive and migratory abilities of cells in each group, respectively. Dual luciferase gene reporting assay was employed to identify the mechanism of miR-188-3p targeting YAP1. Finally, the recovery experiment was performed by co-transfection of miR-188-3p mimics and YAP1 overexpression plasmid in HCC cells. Results The expression level of miR-188-3p was significantly lower in HCC tissues than that in normal liver tissues, and its low expression was closely related to tumor size, tumor differentiation, and TNM stage ( P < 0. 05, respectively). Further survival analysis showed that low miR-188-3p expression level in HCC tissues suggested a poor prognosis (log-rankP = 0. 025). In vitro cell experiments showed that the overexpression of miR-188-3p significantly inhibited the invasion and migration of HCC cells, while inhibition of miR-188-3p expression showed an opposite effect. Dual luciferase reporter gene assay showed that miR-188-3p could inhibit the expression of YAP1 protein by binding to the 3′UTR of YAP1. The results of the recovery experiment confirmed that miR-188-3p inhibited the invasion and migration of HCC cells by inhibiting the expression of YAP1 protein. Conclusion The expression of miR-188-3p is down-regulated in HCC, and miR-188-3p inhibits the invasion and migration of HCC cells by targeting the expression of YAP1, thereby participating in the occurrence and progression of HCC.

Key words: hepatocellular carcinoma, miR-188-3p, YAP1, invasion, migration ,

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