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微小RNA-182通过抑制黑色素瘤中的腺瘤性息肉病蛋白促进细胞增殖和侵袭。

miR-182 promotes cell proliferation and invasion by inhibiting APC in melanoma.

作者信息

Liu Xilin, Li Hong, Wu Guangzhi, Cui Shusen

机构信息

Department of Hand Surgery, China-Japan Union Hospital of Jilin University Changchun, Jilin Province, China.

Department of Rehabilitation, China-Japan Union Hospital of Jilin University Changchun, Jilin Province, China.

出版信息

Int J Clin Exp Pathol. 2018 Apr 1;11(4):1900-1908. eCollection 2018.

Abstract

OBJECTIVE

Common treatment methods have shown a lack of therapeutic effect in melanoma, a type of malignant tumor. The pathogenesis of melanoma is not yet fully clear, therefore, search for a new treatment strategy is urgent. Recent studies have demonstrated that miR-182 is remarkably over-expressed in human melanoma. Our study aimed to explore the underlying mechanism of miR-182 on melanoma.

METHODS

In this study, the expression level of miR-182 was detected using RT-PCR in melanoma and adjacent tissues as well as in HEM-m, A375, A2058, and WM35 cell lines. Functions of miR-182 were investigated by using CCK-8 on cell proliferation, apoptosis, invasion, and cell cycle on A375 cells. Moreover, expression levels of Frz, Dsh, β-catenin, APC, Axin, GSK-3β, and CK1 were detected by Western blotting after knockdown and overexpression of miR-182. Overexpression of miR-182 and knockdown of APC was used to demonstrate regulated functions in melanoma.

RESULTS

Expression levels of miR-182 were significantly upregulated in melanoma tissues and cell lines. Overexpression of miR-182 promoted cell proliferation, migration, and invasion while inhibiting cell apoptosis and cell cycle in S phase. Overexpression of miR-182 upregulated expression levels of β-catenin and APC. Overexpression of miR-182 and knockdown of APC inhibited proliferation of melanoma cells and tumors.

CONCLUSION

Overexpression of miR-182 promotes cell proliferation and invasion by targeting to APC in melanoma. The pathogenesis of miR-182 and APC might provide therapeutic targets for treatment of melanoma in the molecular level.

摘要

目的

常见治疗方法在恶性肿瘤黑色素瘤中显示出治疗效果不佳。黑色素瘤的发病机制尚未完全明确,因此,寻找新的治疗策略迫在眉睫。最近的研究表明,miR-182在人类黑色素瘤中显著过表达。我们的研究旨在探讨miR-182对黑色素瘤的潜在作用机制。

方法

在本研究中,采用RT-PCR检测黑色素瘤组织、癌旁组织以及HEM-m、A375、A2058和WM35细胞系中miR-182的表达水平。通过CCK-8法研究miR-182对A375细胞增殖、凋亡、侵袭及细胞周期的影响。此外,在miR-182敲低和过表达后,通过蛋白质印迹法检测Frz、Dsh、β-连环蛋白、APC、Axin、GSK-3β和CK1的表达水平。采用miR-182过表达和APC敲低来证明其在黑色素瘤中的调控作用。

结果

miR-182在黑色素瘤组织和细胞系中的表达水平显著上调。miR-182过表达促进细胞增殖、迁移和侵袭,同时抑制细胞凋亡及S期细胞周期。miR-182过表达上调β-连环蛋白和APC的表达水平。miR-182过表达和APC敲低抑制黑色素瘤细胞和肿瘤的增殖。

结论

miR-182过表达通过靶向APC促进黑色素瘤细胞增殖和侵袭。miR-182和APC的发病机制可能为黑色素瘤的分子水平治疗提供治疗靶点。

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