MiR-450b-5p enhances the radiosensitivity of HR^(+) and HER2^(−) breast cancer by targeting CDK6  

作　　者：Ruxing Wu Hanwang Zhang Xiaoyuan Huang Liang Zhuang 

机构地区：[1]Reproductive Medicine Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]Cancer Biology Research Centre,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [3]Cancer Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China

出　　处：《Oncology and Translational Medicine》2024年第4期198-203,共6页肿瘤学与转化医学（英文版）

摘　　要：Background:The sensitivity of breast cancer cells to radiation is a key cause of locoregional recurrence after postoperative radiotherapy.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.Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays explored the association between cyclindependent 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 demonstrated 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 tumors 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.

关 键 词：Breast cancer Cyclin-dependent kinase 6 miR-450b-5p RADIOSENSITIVITY 

分 类 号：R737.9[医药卫生—肿瘤]