Song Guo-qing, Zhao Yi
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.
Tumour Biol. 2015 Jul;36(7):5001-9. doi: 10.1007/s13277-015-3151-6. Epub 2015 Feb 14.
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.
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。