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微小RNA-211是细胞周期蛋白磷酸酶25B(CDC25B)表达的直接负调控因子,可抑制三阴性乳腺癌细胞的生长和迁移。

MicroRNA-211, a direct negative regulator of CDC25B expression, inhibits triple-negative breast cancer cells' growth and migration.

作者信息

Song Guo-qing, Zhao Yi

机构信息

Department of Pancreatic and Breast Surgery, Shengjing Hospital of China Medical University, 36 Sanhao Street, Heping District, Shenyang, Liaoning, 110004, People's Republic of China.

出版信息

Tumour Biol. 2015 Jul;36(7):5001-9. doi: 10.1007/s13277-015-3151-6. Epub 2015 Feb 14.

Abstract

The non-coding microRNAs (miRNAs) have tissue- and disease-specific expression patterns. Dysregulation of miRNAs has been associated with initiation and progression of oncogenesis in humans. The abnormal expression of CDC25B phosphatases detected in a number of tumors implies that their dysregulation is involved in malignant transformation. Using miRNA target prediction software, we found that miR-211 could target the 3'UTR sequence of CDC25B. To shed light on their roles of miR-211 in breast cancer, the expression of miR-211 was examined by real-time RT-PCR in breast cancer and normal tissues. MiR-211 is significantly downregulated in breast cancer. MiR-211 re-expression suppressed cell growth, cell cycle, migration, and invasion in triple-negative breast cancer (TNBC) cell line MDA-MB231. Luciferase expression from a reporter vector containing the CDC25B -3'UTR was decreased when this construct was transfected with miR-211. The over-expression of miR-211 suppressed the endogenous CDC25B protein level in TNBC cells. For the first time, we demonstrate that miRNA-211 is a direct negative regulator of CDC25B expression in TNBC cells, alters other related target proteins CCNB1 and FOXM1, and then inhibits breast cancer cells growth, migration, and invasion and lead G2/M arrest. The transcriptional loss of miR-211 and the resultant increase in CDC25B expression facilitate increased genomic instability at an early stage of tumor development.

摘要

非编码微小RNA(miRNA)具有组织和疾病特异性的表达模式。miRNA的失调与人类肿瘤发生的起始和进展相关。在许多肿瘤中检测到的细胞分裂周期蛋白25B(CDC25B)磷酸酶的异常表达表明其失调参与了恶性转化。使用miRNA靶标预测软件,我们发现miR-211可以靶向CDC25B的3'非翻译区(3'UTR)序列。为了阐明miR-211在乳腺癌中的作用,通过实时逆转录聚合酶链反应(RT-PCR)检测了miR-211在乳腺癌组织和正常组织中的表达。miR-211在乳腺癌中显著下调。miR-211的重新表达抑制了三阴性乳腺癌(TNBC)细胞系MDA-MB231中的细胞生长、细胞周期、迁移和侵袭。当含有CDC25B -3'UTR的报告载体与miR-211共转染时,荧光素酶表达降低。miR-211的过表达抑制了TNBC细胞中内源性CDC25B蛋白水平。我们首次证明,miRNA-211是TNBC细胞中CDC25B表达的直接负调节因子,改变其他相关靶蛋白细胞周期蛋白B1(CCNB1)和叉头框蛋白M1(FOXM1),进而抑制乳腺癌细胞的生长、迁移和侵袭,并导致G2/M期阻滞。miR-211的转录缺失以及由此导致的CDC25B表达增加,在肿瘤发生发展的早期阶段促进了基因组不稳定性的增加。

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