miR-3646 promotes cell proliferation, migration, and invasion via regulating G2/M transition in human breast cancer cells

Am J Transl Res. 2016 Apr 15;8(4):1659-77. eCollection 2016.


MicroRNAs (miRNAs) are small non-coding RNAs that are often located in genomic breakpoint regions and play a critical role in regulating a variety of the cellular processes in human cancer. miR-3646 has been reported to take part in tumorigenic progression in breast and bladder cancer, but its potential functions and exact mechanistic roles in breast cancer are still unclear. The objective of this study was to investigate the role of miR-3646 in breast cancer growth and metastasis using both bioinformatic and experimental approaches. Before starting the bench work, we conducted a bioinformatic study to predict the target genes regulated by miR-3646 using a panel of different algorithms. The results showed that miR-3646 might regulate a large number of genes that are related to cell growth, proliferation, metabolis, transport, and apoptosis and some were cancer-related genes. We found that the expression level of miR-3646 was significantly upregulated in breast cancer cells and tissues compared with normal breast cells and no tumor tissues. Subsequently, the MTT and colony formation assay results showed that up-regulation of miR-3646 promoted the cell viability and proliferation. Our results also showed that down-regulation of miR-3646 arrested the cells in G2/M phase in MCF7 and MDA-MB-231 cells which was accompanied by the down-regulation of CDK1/CDC2 and cyclin B1 and upregulation of p21Waf1/Cip1, p27 Kip1, and p53, suggesting that down-regulation of miR-3646 induces G2/M arrest through activation of the p53/p21/CDC2/cyclin B1 pathway. In addition, overexpression of miR-3646 promoted migration and invasion of MCF7 and MDA-MB-231 cells. Taken together, miR-3646 is a potential oncogene in breast cancer and it may represent a new niomarker in the diagnosis and prediction of prognosis and therapeutic response.

Keywords: bioinformatics; breast cancer; invasion; miR-3646; migration; proliferation.