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miR-183 通过靶向 AXIN2 维持经典 Wnt 信号活性并调节膀胱癌的生长和凋亡。

MiR-183 maintains canonical Wnt signaling activity and regulates growth and apoptosis in bladder cancer via targeting AXIN2.

机构信息

Department of Urology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou City, Fujian Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Aug;22(15):4828-4836. doi: 10.26355/eurrev_201808_15618.

DOI:10.26355/eurrev_201808_15618
PMID:30070321
Abstract

OBJECTIVE

Previous investigations have shown that miR-183 is upregulated in bladder cancer (BC); however, its biological significance is not fully investigated. The goal of the current study is to analyze the function of miR-183 in BC development and progression.

PATIENTS AND METHODS

23 pairs of BC tumor and adjacent tissues were analyzed for miR-183 and c-Myc expression using Real-time polymerase chain reaction (PCR). MiR-183 expression was modulated by transfection of miR-183 or miR-183 inhibitor (miR-183-in). Protein expression of AXIN2, c-Myc and Cyclin D1 was determined by western blot. Cell growth activity and apoptotic potential were evaluated by cell viability assay and flow cytometry assay, respectively. Luciferase activity assay was conducted to determine whether AXIN2 is a direct target of miR-183.

RESULTS

The expression of miR-183 is upregulated in BC tissues and cell lines, and is positively correlated with the expression of the Wnt target gene, c-Myc. MiR-183 positively regulated Wnt signaling activity by directly suppressing its negative feedback regulator, AXIN2. Overexpression of miR-183 promoted cell growth and inhibited apoptosis. Inhibition of miR-183 attenuated cell growth and enhanced apoptosis. The effect of miR-183 on cell growth and apoptosis can be abolished by knockdown of AXIN2.

CONCLUSIONS

MiR-183 functions as an oncomiR in BC and upregulates Wnt signaling activity by directly suppressing AXIN2 expression.

摘要

目的

先前的研究表明 miR-183 在膀胱癌(BC)中上调;然而,其生物学意义尚未完全研究。本研究的目的是分析 miR-183 在 BC 发展和进展中的功能。

患者和方法

使用实时聚合酶链反应(PCR)分析 23 对 BC 肿瘤和相邻组织中的 miR-183 和 c-Myc 表达。通过转染 miR-183 或 miR-183 抑制剂(miR-183-in)来调节 miR-183 的表达。通过 Western blot 测定 AXIN2、c-Myc 和 Cyclin D1 的蛋白表达。通过细胞活力测定和流式细胞术分别评估细胞生长活性和凋亡潜能。进行荧光素酶活性测定以确定 AXIN2 是否是 miR-183 的直接靶标。

结果

miR-183 在 BC 组织和细胞系中表达上调,并与 Wnt 靶基因 c-Myc 的表达呈正相关。miR-183 通过直接抑制其负反馈调节剂 AXIN2 来正向调节 Wnt 信号活性。miR-183 的过表达促进细胞生长并抑制细胞凋亡。miR-183 抑制细胞生长和增强细胞凋亡的作用可通过 AXIN2 的敲低而被废除。

结论

miR-183 在 BC 中作为致癌 miRNA 发挥作用,并通过直接抑制 AXIN2 表达来上调 Wnt 信号活性。

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