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微小RNA-186通过靶向Twist1抑制乳腺癌细胞的增殖、迁移和上皮-间质转化。

miR-186 inhibits proliferation, migration, and epithelial-mesenchymal transition in breast cancer cells by targeting Twist1.

作者信息

Sun Wen-Juan, Zhang Ya-Na, Xue Peng

机构信息

Department of General Surgery, Qingdao West Coast New Area Central Hospital, Qingdao, Shandong, China.

Department of Anesthesiology, Qingdao West Coast New Area Central Hospital, Qingdao, Shandong, China.

出版信息

J Cell Biochem. 2019 Jun;120(6):10001-10009. doi: 10.1002/jcb.28283. Epub 2018 Dec 14.

Abstract

OBJECTIVE

Breast cancer (BC) is the most prevalent malignancy in women worldwide. Our study aimed to investigate the expression and biological effect of miR-186 in BC.

METHODS

Expression of miR-186 was determined by quantitative reverse transcription PCR. Kaplan-Meier curves were calculated for the survival data analysis. Functional assays were performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound healing assay. Protein expression was analyzed by Western blot.

RESULTS

miR-186 was downregulated in BC tissues and cells. Downregulation of miR-186 was associated with tumor metastasis and a poor overall survival in patients with BC. Overexpression of miR-186 inhibited BC cells proliferation, migration, and epithelial-mesenchymal transition process; while suppression of miR-186 exhibited an opposite effects on BC cells. In addition, Twist1 was identified as a direct target of miR-186 in BC and restoration of Twist1 attenuated the biological effect of miR-186 on BC cells.

CONCLUSION

Our findings suggest that miR-186 functions as a tumor suppressor by targeting Twist1 in BC. miR-186 may serve as a novel biomarker in BC diagnosis or a new therapeutic target in BC treatment.

摘要

目的

乳腺癌(BC)是全球女性中最常见的恶性肿瘤。我们的研究旨在探讨miR-186在BC中的表达及生物学效应。

方法

通过定量逆转录PCR测定miR-186的表达。计算Kaplan-Meier曲线用于生存数据分析。通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和伤口愈合试验进行功能测定。通过蛋白质印迹分析蛋白质表达。

结果

miR-186在BC组织和细胞中表达下调。miR-186的下调与BC患者的肿瘤转移和总体生存率差有关。miR-186的过表达抑制BC细胞增殖、迁移和上皮-间质转化过程;而抑制miR-186对BC细胞表现出相反的作用。此外,Twist1被鉴定为BC中miR-186的直接靶点,Twist1的恢复减弱了miR-186对BC细胞的生物学效应。

结论

我们的研究结果表明,miR-186在BC中通过靶向Twist1发挥肿瘤抑制作用。miR-186可能作为BC诊断中的新型生物标志物或BC治疗中的新治疗靶点。

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