MicroRNA Let-7a Inhibits Cell Proliferation, Migration And Invasion By Targeting MAGE-A1 In Breast Cancer

MicroRNA(miRNA)is a new class of non-coding small RNA molecules,which can regulate post-transcriptional of genes and plays a key role in the occurrence and development of many tumors.In all human cancer-related mi RNAs,let-7a has attracted the most interest due to their aberrant expression in human cancers.Meanwhile melanoma-related antigen A(MAGE-A)family are characterized by a unique pattern of tissue expression,aberrantly expressed in a wide variety of tumors but absent from normal adult tissues.Studies have shown that the expression of MAGE-A1 as oncogenes have increased the risk of recurrence and mortality for breast cancer patients.However,as a tumor suppressor,whether let-7a regulated MAGE-A1 in breast cancer worth to be further studied.Objective: To investigate whether Let-7a can play a tumor suppressor by targeting MAGE-A1 in breast cancer,then control the metastasis and recurrence,also provide a new target for the treatment of breast cancer.Methods: The tumor tissues(n=65),were obtained from the department of Breast Center,the fourth hospital of Hebei Medical University.Let-7a and MAGE-A1 expression in breast tissues were examined by q RT-PCR.Let-7a and MAGE-A1 expression in MDA-MB-231 and MCF-7 were examined by RT-qPCR and Western blot.breast cancer cells proliferation,migration and invasion were assessed by in vitro cell culture experiments.Dual-luciferase reporter was used to demonstrated that let-7a targets MAGE-A1.Results:1.Let-7a and MAGE-A1 expression in breast cancer tissues and their relationshipThe expression level of let-7a was significantly lower in breast cancer patients with larger tumor or higher histological grade(P=0.049 and P=0.041).However,there was no significant difference in other groups(P ≥ 0.05).MAGE-A1 was expressed in 33 tissues with a positive rate of 50.8%(33/65).MAGE-A1 expression was no significant difference in each subgroup(P ≥0.05).In the samples with positive expression of MAGE-A1,the expression level was negatively correlated with let-7a(P=0.008).2.Let-7a inhibits proliferation,migration and invasion of breast cancer cell linesIn the cells transfected with let-7a mimics,CCK-8 assay,cell scratch assay and Transwell invasion assay showed that cell proliferation,migration and invasion were significantly reduced.In contrast,there was a significant increase in let-7a inhibitor transfected cells.3.Let-7a targeting MAGE-A1 inhibits its expression at nucleic acid and protein levelsRT-qPCR and Western blotting experiments showed that let-7a and MAGE-A1 were negatively correlated at the nucleic acid and protein levels.Dual-luciferase reporter assays showed that let-7a was targeted to the 451-457 locus of the 3’UTR of MAGE-A1 mRNA.4.Let-7a inhibits cell proliferation,migration and invasion by targeting MAGE-A1 in breast cancer cell linesThe let-7a mimics NC,let-7a mimics,let-7a mimics and MAGE-A1 vectors were transfected into the MDA-MB-231 cell line.The CCK-8 assay,cell scratch assay and Transwell invasion assay showed that let-7a inhibits cell proliferation,migration and invasion by targeting MAGE-A1.Conclusions:1.The expression of Let-7a in breast cancer tissues are negatively correlated with the expression of MAGE-A1,and its low expression is related to the proliferation and invasion of breast cancer.2.Let-7a inhibits cell proliferation,migration and invasion by targeting MAGE-A1 in breast cancer cell lines,providing a new target for the treatment of breast cancer.