MiRNA-106a Promotes The Growth Of Transplanted Breast Cancer And Decrease The Sensitivity Of Transplanted Tumor To Cisplatin

Background:In the world,in women breast cancer is one of the most common malignant tumors,and it is also one of the tumors with the highest mortality rate.Understanding the molecular mechanism of recurrence and metastasis of breast cancer will help to improve the long-term prognosis of breast cancer.Microrna-106 a,located on chromosome xq26.2,had been proved to be involved in the occurrence,progression and drug resistance of a variety of tumors.The expression of microrna-106 a was significantly increased in gastric cancer and ovarian cancer,but decreased in renal cell carcinoma,glioma and astrocytoma.However,there are few reports about the role and mechanism of microrna-106 a in the development of breast cancer.Previous studies had confirmed that microrna-106 a could promote the proliferation,invasion and metastasis of breast cancer.This study aims to investigate the effects of micro RNA-106 a on the growth and chemosensitivity of breast cancer xenografts in nude mice,and to explore whether micro RNA-106 a plays a role through Wnt signaling pathway.Objective:To explore the effect of micro RNA-106 a on the growth of breast cancer xenografts and the sensitivity of chemotherapeutic agents.Methods:Breast cancer cell lines(MDA-MB231 and MCF7)were transfected with an micro RNA-106 a mimic and micro RNA-106 a inhibitor.BALB/c female nude mice were selected to construct a transplanted-tumor model.Cisplatin treatment was performed 2 weeks after inoculation.After 5 weeks,tumor tissue was weighed.Apoptosis of tumor cells was detected by TUNEL staining.The expression of these proteins(Ki67,β-catenin,cyclin D1 and c Myc)was detected by immunohistochemistry.The contents of P53,RUNX3,ABCG2,β-catenin,BAX,and BCL2 m RNA were detected by q RT-PCR.Results:The micro RNA-106 a mimic(MM)group’s tumor volume and weight were significantly bigger than those of the model group(p<0.05).micro RNA-106 a m RNA content was higher than the blank control group(p<0.05),and β-catenin and Ki67 protein were strongly positive(p<0.05).β-catenin,BCL2,and ABCG2 m RNA content was were increased(p<0.05).P53,BAX,and RUNX3 m RNA content was decreased(p < 0.05).The number of positive cells on TUNEL staining was significantly lower in the mi R106 a inhibitor(MI)group(p<0.05).After cisplatin treatment,inhibition of tumor growth was most obvious in the MI+DDP(cisplatin)group(p<0.05).Compared with the MM group,tumor growth in the MM+FH535(Wnt-pathway inhibitor)group was significantly lower(p<0.05),and Wnt-pathway activity was decreased(p<0.05).Conclusion:Overexpression of micro RNA-106 a can promote the growth of transplanted breast cancer and decrease the sensitivity of transplanted tumors to cisplatin.The mechanism may be related to abnormal activation of the Wnt-signaling pathway.