Overexpression of MicroRNA-9 inhibits proliferation of human breast cancer cells by targeting STAT3
Purpose: To study the role and therapeutic potential of miR-9 in the treatment of breast cancer.
Methods: The expression of miR-9 was evaluated in breast cancer cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, while cell migration was assessed by wound healing assay. Transfections were performed with Lipofectamine 2000 reagent. Overexpression of miR-9 was performed by transfecting breast cancer cells with miR-9 mimics, and suppression of STAT3 was done with Si-RNA construct. Target identification was carried out using target scan, while protein expression was determined with immunoblotting.
Results: The results revealed that miR-9 was significantly (p < 0.05) downregulated in the breast cancer cell lines. Overexpression of miR-9 significantly (p < 0.05) inhibited the proliferation of the breast cancer cells by initiation of apoptosis and cell cycle arrest. In addition, MiR-9 overexpression inhibited the migration of the breast cancer cells. TargetScan analysis showed that STAT3 was the potential target of miR-9: it was significantly downregulated in breast cancer cells overexpressing miR-9. Silencing of STAT3 exerted inhibitory effects on the proliferation and migration of breast cancer cells similar to that of miR-9 overexpression.
Conclusion: MiR-9 regulates the proliferation of human breast cancer by targeting STAT3. Hence, miR-9 can be potentially applied as a therapeutic agent for the management of breast cancer.
Keywords: Breast cancer, MicroRNA-9, STAT3, Apoptosis, Bioinformatic analysis