摘要Background:The sensitivity of breast cancer cells to radiation is a key cause of locoregional recurrence after postoperative radiother-apy.Several studies have reported that microRNAs (miRNAs) are involved in the radiosensitivity of human breast cancer cells.One miRNA microarray study showed that miR-450b-5p was overexpressed 13.3-fold in patients with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer and no local relapse compared with local relapse patients.However,its underlying mechanism of action remains unknown.Methods:The predicted target mRNAs of miR-450b-5p were screened using the TargetScan,miRDB,and miRWalk databases.West-ern blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays explored the association between cyclin-dependent kinase 6 (CDK6) and miR-450b-5p.The cell counting kit-8 assay and flow cytometry detected the proliferation of transfected MCF7 cells.Colony formation and xenograft tumors detected the radiosensitivity of the transfected MCF7 cells.Results:Bioinformatics analysis,Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays demon-strated that CDK6 was the target gene of miR-450b-5p.Furthermore,in vitro and in vivo experiments showed that miR-450b-5p inhibited MCF7 cell proliferation and cell cycle progression,increased the sensitizer enhancement ratio,and decreased the volume of xenograft tu-mors after irradiation by regulating CDK6.Conclusions:This study demonstrates that miR-450b-5p enhances the radiosensitivity of hormone receptor-positive (HR+) and HER2-breast cancer cells and elucidates its mechanism.miR-450b-5p may be considered a therapeutic target in HR+and HER2-breast cancer treated with radiotherapy.
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