MiR-145-targeted HBXIP modulates human breast cancer cell proliferation.

BACKGROUND: MiR-145 has been identified as a tumor suppressive microRNA in multiple cancers. In this current investigation, we searched for new direct targets of miR-145 and evaluated their effect on breast cancer development.

METHODS: Targetscan was used to predict the target genes of miR-145. The targeting of miR-145 on oncogenic HBXIP was verified by luciferase reporter gene analysis. The effect of miR-145 on the level of messenger RNA and protein of HBXIP was evaluated by quantitative real-time PCR and immunoblotting. Correlations between miR-145 and HBXIP, as well as miR-145 expression, were analyzed in 30 paired breast cancer and noncancerous tissues by quantitative real-time PCR. Methyl thiazol tetrazolium and colony formation assays were applied to determine the cell proliferation ability.

RESULTS: HBXIP was identified as a novel target gene of miR-145 in breast cancer. MiR-145 was found to dose-dependently decrease messenger RNA and protein expression of HBXIP in breast cancer MCF-7 cells. Notably, miR-145 expression was negatively related to HBXIP expression and was obviously reduced in breast cancer samples. Finally, miR-145 suppressed cell proliferation while its inhibitor, anti-miR-145, accelerated cell proliferation. Interestingly, silencing of HBXIP reversed the acceleration of cell proliferation induced by anti-miR-145 in breast cancer.

CONCLUSION: Oncogenic HBXIP is a new direct target of tumor suppressive miR-145. Our findings reveal that miR-145-targeting HBXIP could be a potential therapeutic target in breast cancer.