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miR-205 通过抑制 YAP1 促进宫颈癌细胞凋亡并增强顺铂的药物敏感性。

miR-205 Promotes Apoptosis of Cervical Cancer Cells and Enhances Drug Sensitivity of Cisplatin by Inhibiting YAP1.

机构信息

Department of Gynecology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

Department of Genetics, Qiqihar Medical University, Qiqihar, China.

出版信息

Cancer Biother Radiopharm. 2020 Jun;35(5):338-344. doi: 10.1089/cbr.2019.2983. Epub 2020 May 5.

Abstract

Elevated expression of Yes-associated protein (YAP1) involves in the pathogenesis of cervical cancer. Bioinformatics analysis showed a targeting relationship between miR-205 and the 3'-UTR of YAP1. In this study, we aim to explore the role of miR-205 in the proliferation, apoptosis, or cisplatin (CDDP) resistance of cervical cancer cells. The dual luciferase reporter gene assay verified the relationship between miR-205 and YAP1. The CDDP-resistant cell line Hela/CDDP cells were cultured and divided into miR-NC group, miR-205 mimic group, and miR-205 inhibitor group followed by analysis of the expression of miR-205 and YAP1 mRNA by quantitative real-time polymerase chain reaction (qRT-PCR), and YAP1 protein level by western blot. There was a targeted relationship between miR-205 and YAP1 mRNA. Compared with cervical cell line HCerEpiC cells, miR-205 expression was significantly decreased and YAP1 mRNA and protein expression was significantly increased in Hela cells ( < 0.01). Compared with miR-NC group, YAP1 protein expression in HeLa/CDDP cells was significantly decreased, cell apoptosis was increased, and proliferation was inhibited in miR-205 mimic-transfected Hela/CDDP cells ( < 0.01). Opposite results were obtained in miR-205 inhibitor-transfected Hela/CDDP cells. The expression of miR-205 is related to the CDDP resistance of cervical cancer cells. Increasing the expression of miR-205 can downregulate the expression of YAP1, inhibit the proliferation and promote apoptosis of cervical cancer cells, and enhance the sensitivity to CDDP.

摘要

Yes 相关蛋白(YAP1)的高表达参与宫颈癌的发病机制。生物信息学分析显示 miR-205 与 YAP1 的 3'-UTR 之间存在靶向关系。本研究旨在探讨 miR-205 在宫颈癌细胞增殖、凋亡或顺铂(CDDP)耐药中的作用。双荧光素酶报告基因检测验证了 miR-205 与 YAP1 之间的关系。培养 CDDP 耐药细胞系 Hela/CDDP 细胞,并分为 miR-NC 组、miR-205 模拟物组和 miR-205 抑制剂组,然后通过定量实时聚合酶链反应(qRT-PCR)分析 miR-205 和 YAP1 mRNA 的表达,以及 Western blot 分析 YAP1 蛋白水平。miR-205 与 YAP1 mRNA 之间存在靶向关系。与宫颈细胞系 HCerEpiC 细胞相比,Hela 细胞中 miR-205 表达明显降低,YAP1 mRNA 和蛋白表达明显升高(<0.01)。与 miR-NC 组相比,miR-205 模拟物转染的 Hela/CDDP 细胞中 YAP1 蛋白表达明显降低,细胞凋亡增加,增殖受到抑制(<0.01)。在转染 miR-205 抑制剂的 Hela/CDDP 细胞中则得到了相反的结果。miR-205 的表达与宫颈癌细胞的 CDDP 耐药性有关。增加 miR-205 的表达可以下调 YAP1 的表达,抑制宫颈癌细胞的增殖并促进凋亡,并增强对 CDDP 的敏感性。

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