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miR-181a 通过抑制宫颈癌细胞中的骨桥蛋白促进细胞凋亡并降低顺铂耐药性。

MiR-181a Promotes Apoptosis and Reduces Cisplatin Resistance by Inhibiting Osteopontin in Cervical Cancer Cells.

机构信息

Department of Obstetrics and Gynecology, Lishui Hospital of Traditional Chinese Medicine, Lishui, Zhejiang, China.

Department of Gynecology, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu, China.

出版信息

Cancer Biother Radiopharm. 2019 Nov;34(9):559-565. doi: 10.1089/cbr.2019.2858. Epub 2019 Aug 22.

Abstract

In this study, the authors established a cervical cancer cisplatin (DDP) drug-resistant cell line to explore the role of miR-181a in the regulation of osteopontin (OPN) expression and the proliferation, apoptosis, as well as DDP resistance of cervical cancer cells. Dual luciferase reporter gene assay was performed to validate the targeted relationship between miR-181a and OPN. The DDP-resistant cell line CaSki/DDP was established to compare the expressions of miR-181a and OPN. The cell proliferation activity was detected by CCK-8 assay. CaSki/DDP cells were divided into miR-NC group and miR-181a mimic group followed by analysis of cell apoptosis by flow cytometry, and the cell proliferation by EdU staining. There was a targeted relationship between miR-181a and OPN mRNA. MiR-181a expression was significantly lower, while OPN mRNA and protein levels were significantly higher in CaSki/DDP cells than that in CaSki cells. Compared with the miR-NC group, OPN mRNA and protein were significantly decreased, cell apoptosis was significantly increased, and cell proliferation ability was significantly attenuated in miR-181a mimic transfection group. The decrease of miR-181a expression and the upregulation of OPN expression are related to the DDP resistance of cervical cancer cells. Overexpression of miR-181a can inhibit the expression of OPN, induce cell apoptosis cells, restrain cell proliferation, and reduce DDP resistance in cervical cancer cells.

摘要

在这项研究中,作者建立了宫颈癌顺铂(DDP)耐药细胞系,以探讨 miR-181a 在调节骨桥蛋白(OPN)表达以及宫颈癌细胞增殖、凋亡和 DDP 耐药中的作用。双荧光素酶报告基因检测验证了 miR-181a 与 OPN 之间的靶向关系。建立了宫颈癌耐药细胞系 CaSki/DDP 来比较 miR-181a 和 OPN 的表达。通过 CCK-8 检测评估细胞增殖活性。将 CaSki/DDP 细胞分为 miR-NC 组和 miR-181a 模拟物组,然后通过流式细胞术分析细胞凋亡,通过 EdU 染色分析细胞增殖。miR-181a 与 OPN mRNA 之间存在靶向关系。与 CaSki 细胞相比,CaSki/DDP 细胞中 miR-181a 表达明显降低,而 OPN mRNA 和蛋白水平明显升高。与 miR-NC 组相比,miR-181a 模拟物转染组中 OPN mRNA 和蛋白明显降低,细胞凋亡明显增加,细胞增殖能力明显减弱。miR-181a 表达降低和 OPN 表达上调与宫颈癌细胞的 DDP 耐药有关。miR-181a 的过表达可以抑制 OPN 的表达,诱导细胞凋亡,抑制细胞增殖,并降低宫颈癌细胞的 DDP 耐药性。

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