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miR-155 通过调控 GSK-3β/β-catenin 通路影响膀胱癌细胞的增殖和凋亡。

MiR-155 affects proliferation and apoptosis of bladder cancer cells by regulating GSK-3β/β-catenin pathway.

机构信息

Department of Urology, Key Laboratory of Gansu Province for Urological Diseases, Department of Urology of Lanzhou University Second Hospital, Urology institute of Lanzhou University Second Hospital, Lanzhou, Gansu, P.R. China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5682-5690. doi: 10.26355/eurrev_201907_18305.

Abstract

OBJECTIVE

GSK-3β negatively regulates Wnt/β-catenin signaling pathway. The abnormal miR-155 expression is associated with bladder cancer. Bioinformatics analysis revealed a complementary binding site between miR-155 and GSK-3β mRNA. This study investigated the role of miR-155 in the proliferation and apoptosis of bladder cancer cells.

PATIENTS AND METHODS

The dual luciferase reporter gene assay validated the targeted regulation between miR-155 and GSK-3β. Tumor tissues and adjacent tissues were collected from bladder cancer patients and the expression of miR-155 and GSK-3β mRNA was detected by RT-PCR. Bladder cancer cell line BIU-87 cells were cultured in vitro and divided into miR-NC group and miR-155 inhibitor group. The expressions of miR-155, GSK-3β and β-catenin were compared, cell apoptosis was detected by flow cytometry, and cell proliferation was detected by EdU staining.

RESULTS

Compared with adjacent tissues, miR-155 expression was significantly increased in bladder cancer tissues, and GSK-3β mRNA expression was significantly decreased. There was a targeted regulatory relationship between miR-155 and GSK-3β. Compared with SV-HUC-1 cells, miR-155 expression in bladder cancer BIU-87 and 5637 cells was significantly increased, and GSK-3β expression was significantly decreased. Transfection of miR-155 inhibitor significantly increased GSK-3β expression in BIU-87 and 5637 cells, decreased β-catenin expression, increased cell apoptosis, and decreased cell proliferation.

CONCLUSIONS

The increased expression of miR-155 plays a role in reducing the expression of GSK-3β and in promoting the pathogenesis of bladder cancer. Inhibition of miR-155 can up-regulate the expression of GSK-3β, inhibit the activity of Wnt/β-catenin pathway, attenuate proliferation and promote apoptosis of bladder cancer cells.

摘要

目的

GSK-3β 负调控 Wnt/β-catenin 信号通路。异常的 miR-155 表达与膀胱癌有关。生物信息学分析显示 miR-155 和 GSK-3β mRNA 之间存在互补结合位点。本研究探讨了 miR-155 在膀胱癌细胞增殖和凋亡中的作用。

患者与方法

双荧光素酶报告基因检测验证了 miR-155 与 GSK-3β 之间的靶向调控关系。收集膀胱癌患者的肿瘤组织和相邻组织,采用 RT-PCR 检测 miR-155 和 GSK-3β mRNA 的表达。体外培养膀胱癌 BIU-87 细胞,分为 miR-NC 组和 miR-155 抑制剂组。比较 miR-155、GSK-3β 和 β-catenin 的表达,流式细胞术检测细胞凋亡,EdU 染色检测细胞增殖。

结果

与相邻组织相比,膀胱癌组织中 miR-155 表达明显升高,GSK-3β mRNA 表达明显降低。miR-155 与 GSK-3β 存在靶向调控关系。与 SV-HUC-1 细胞相比,膀胱癌 BIU-87 和 5637 细胞中 miR-155 表达明显升高,GSK-3β 表达明显降低。转染 miR-155 抑制剂可显著上调 BIU-87 和 5637 细胞中 GSK-3β 的表达,降低 β-catenin 的表达,增加细胞凋亡,减少细胞增殖。

结论

miR-155 的表达增加在降低 GSK-3β 表达和促进膀胱癌发病机制中起作用。抑制 miR-155 可上调 GSK-3β 的表达,抑制 Wnt/β-catenin 通路的活性,减弱膀胱癌细胞的增殖并促进其凋亡。

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