The Influence Of MR-34a On Biological Behavior Of Breast Cancer And Its Chemosensitivity

Breast cancer is one of the highest incidence of malignant tumors in women.In recent years,with the development of modern medical molecular diagnostics,substantial progress has been made in the early diagnosis and treatment of breast cancer,but rate of refractory and high recurrence is still an urgent need to be addressed.Therefore,the search for new and feasible diagnosis and treatment method has always been the focus and hot spots of breast cancer research.A miRNA is a non-coding RNA with a length of about 22 nt which acts as a negative regulator of the target gene by pairing the 3’UTR of the specific target gene through the base complementary pairing principle,and the miRNA regulates the expression level of genes in the transcriptional level,that is,the degradation of certain mRNA and inhibition of the synthesis protein.An increasing number of recent studies have found that miR-3 4a plays an important regulatory role in the development and progression of various malignant cancers such as colon cancer,malignant glioma and lung carcinoma,but there is little research on the progress of breast cancer.This study focused on the expression of miR-34a in breast cancer and its effect on the biological function of breast cancer cells and the possible mechanism,and discussed the mechanism of miR-34a on breast cancer chemotherapy sensitivity.Objective:To investigate the relationship of miR-34a and breast cancer patients’clinicopathological parameter.To investigate the influence of miR-34a on breast cancer tissues and cells,and its possible mechanism,and analysis the mechanism of miR-34a on the breast cancer chemosensitivity,which may provide substantial rationale for tailored therapy of breast cancer.Methods:The expression of miR-34a in breast cancer tissues and matched adjacent mucosa were measured by RT-PCR.We analyzed the correlation of miR-34a expression and the clinical data of breast cancer patients.Then we analyzed the prognosis of breast cancer patients and miR-34a expression using Kaplan-Meier survivorship curve.We also detected the miR-34a expression of breast cancer cells,and its influence on proliferation,apoptosis,cell cycle and migration of breast cancer cell lines transfected by miR-34a mimics.And we verified Wntl as the target gene of miR-34a by dual-luciferase methods.The expression of Wntl decreased in Breast cancer cell lines transfected by miR-34a mimics were detected by Western blotting.And then we detected the expression of Wntl downstream target gene(β-catenin、Cyclin D1).At last,MCF-7 cells was treated by miR-34a,paclitaxel and together with miR-34a and paclitaxel.We used the CCK-8 assay to detect the breast cancer cell MCF cell proliferation.Western blot method was used to examine the expression of ALDH1.Then we used the mammosphere formation assays to detect the self-renewal ability of breast cancer stem cells.Results:miR-34a in breast cancer cell lines and tissues were high-expression compare to normal breast tissues and cells.The expression level of miR-34a in breast cancer tissues were related to clinical stages and lymphatic metastasis.Overexpression of miR-34a in Breast cancer cell lines could inhibit the breast cancer cells proliferation,migration and invasion.Meanwhile,the expression of Wntl was inhibited by miR-34a,further research indicated Wntl is the target protein of miR-34a by dual-luciferase experiment,and the expression of Wntl downstream target gene((3-catenin.Cyclin D1)were inhibited too.The combination group can inhibit proliferation of MCF-7 cells significantly compared with paclitaxel alone group and miR-34a mimics group.While the expressions of ALDH1 and the mammosphere formation ability decreased significantly in MCF-7 cells with the miR-34a overexpressing when treated with paclitaxel compared with the other groups.Conclusion:miR-34a is down-regulated in breast cancer tissues and cells,and miR-34a may participate in the cell proliferation,migration and invasion of breast cancer cell lines,and the possible mechanism is targeting effect on Wntl gene.And that our results indicated miR-34a could provide an efficient approach for breast cancer therapy by targeting Wntl signaling pathways,and enhance the chemosensitivity of paclitaxel on breast cancer.