MiR-634 Decreases the Radioresistance of Human Breast Cancer Cells by Targeting STAT3.

Abstract

Background: Breast cancer is the second most common cancer in women, which is usually treated by radiation therapy. However, resistance of cancer cells to radiation therapy has made treatment difficult. Therefore, finding effective ways to reduce the radiation resistance of cancer cells is an urgent problem to be solved. Materials and Methods: MCF-7 and MDA-MB-231 cells (on accepting radiation) were established to model radiation resistance, namely MCF-7/R and MDA-MB-231/R. The authors then examined the expression of miR-634 through quantitative reverse transcription-polymerase chain reaction. MCF-7/R and MDA-MB-231/R cells were transfected with overexpressed miR-634 mimics. In addition, TargetScan predicted which binding site was targeted by miR-634, and luciferase assay detected the signal transducer and activator of transcription 3 (STAT3) 3'UTR luciferase activity after transfection of mimics expressing miR-634 into HEK-293 cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and western blot assays were used for examination of different levels of biological function. Results: miRNA-634 expression was significantly decreased in radiated MCF-7 and MDA-MB-231 cells. When miR-634 mimic was transfected into radiation-resistant MCF-7/R and MDA-MB-231/R cells, the survival rate of radiation-tolerant cells was significantly reduced. Moreover, STAT3 was found to directly interact with miR-634, and further studies demonstrated that miR-634 negatively regulated STAT3. Conclusion: miR-634 was able to regulate STAT3 and enhance the sensitivity of breast cancer cells to radiation; these results might shed new light on radiation therapy for breast cancer.