关键词: 乳腺肿瘤, 共济失调一毛细血管扩张突变基因, 顺铂, miR-18b

Abstract:

Objective To investigate the effect of miR-18b on the chemosensitivity of human breast cancer MDA-MB-231 cells,and to elucidate its possible mechanism.Methods The breast cancer MDA-MB-231 cells were divided into MDA-MB-231 group,MDA-MB-231+DDP group,MDA-MB-231-NC group,MDA-MB-231-NC+DDP group,MDA-MB-231 mimic group,and MDA-MB-231 mimic+DDP group.The target gene of miR-18b was predicted by bioinformatics method;Dual-luciferase Reporter Assay was used to demonstrate the binding of miR-18b 3' UTR of targets;Western blotting method was used to analyze the expression levels of ATM protein;qRT-PCR method was used to detect the expression levels of miR-18b in MDA-MB-231 cells;CCK-8 method was used to detect the inhibitory rate of growth of MDA-MB-231 cells.Results The Luciferase results showed that the ATM was the target gene of miR-18b-MB-231,which combined with the ATM 3'UTR sequence part;compared with MDA-MB-231 group, the expression levels of miR-18b in the MDA-MB-231 cells in MDA-MB-231 mimic group and MDA-MB-231 mimic+DDP group were increased(P<0.05).The Western blotting results showed that comared with MDA-MB-231 group,the expression level of ATM protein in MDA-MB-231 group was increased(P<0.05).Compared with MDA-MB-231-NC group,the expression level of ATM protein of the cells in MDA-MB-231 mimic group was decreased(P<0.05);compared with MDA-MB-231-NC+DDP group,the expression level of ATM protein of the cells in MDA-MB-231 mimic+DDP group was decreased(P<0.05).The CCK-8 results showed that compared with MDA-MB-231-NC group,after treated with different concentrations of DDP,the inhibitory rates of the proliferation of the cells in MDA-MB-231 mimic group were increased.Conclusion miR-18b can enhance the chemosensitivity of human breast cancer MDA-MB-231 cells to DDP through target-regulating ATM protein.

Key words: breast neoplasms, ataxia-telangiectasia mutated gene, cisplatin, miR-18b