MiRNA-4312 Promotes Proliferation And Inhibits Apoptosis In Mammary Epithelial Cell

Breast cancer is a serious threat to women's health and pathogenesis of the disease is complex,affected by multiple factors.In recent years,the role of miRNA in the development of cancers has attracted more and more attention.miRNA is an endogenous non-coding small RNA,being involved in regulation of gene expression.It has been shown that abnormal expression of miRNAs is associated with tumorigenensis.Previous studies have shown that a series of miRNAs are involved in occurrence and development of the breast cancer.The miR-21,miR-155,miR-182,miR-10 b,miR-27 a and miR-9 are served as oncogenes while the let-7 family,miR-200 family,miR-205,miR-335,miR-145 and miR-19 have inhibitory effects on tumorigenesis.However,the functioning mechanisms of many miRNAs in breast cancer development remains unclear.In order to clarify roles of miRNA in development of breast cancer,we screened miRNAs in both breast cancer patient serum and breast cancer cells.We found a series of miRNAs with differences in expressions,the results were further confirmed by qPCR in the breast caner cells.One of these miRNAs,miR-4312,is a novel due to the function of miR-4312 on breast cancer development have not well studied.Here we showed that overexpression of miR-4312 in the MCF-10 A cell led to a promotion of cell proliferation,apoptosis and migration.The overexpression of miR-4312 in the MCF-10 A resulted in:(i)the cell growth was faster relative to the control;(ii)cells in G0/G1 phase were largely decreased while cells in G2/M phase were significantly increased;(iii)the number of apoptotic cells decreased obviously but cell migration was enhanced.It was found that the protein expression level of MCM2(DNA helicase)and Caspase 3,BCL2 and PARP1 was significantly increased.These results indicate that miR-4312 promotes cell proliferation and migration but inhibits apoptosis.Additionally,overexpression of miR-4312 significantly reduced luciferase activity of wild-type PDCD4 3'UTR,indicating that PDCD4 gene is the target gene of miR-4312.It has been shown that PDCD4 is a tumor suppressor gene.When PDCD4 was silenced by siRNA in MCF-10 A cells,the growth rate was also largely increased;and cells in G0/G1 phase and the apoptotic cells were significantly decreased while these in S phase were increased.The results indicate that down-expression of PDCD4 also promotes cell proliferation and inhibit apoptosis.These results are consistent with the observations in the presence of overexpressed miR-4312 in MCF-10 A cells.It is likely that the miR-4312 molecule in breast cancer promotes cell proliferation and inhibits cell apoptosis by regulating the expression level of the PDCD4 protein.