MicroRNA-26a Inhibits Cell Proliferation,invasion And Enhances Docetaxel Sensitivity By Targeting FAM98A In Breast Cancer

Objective: MicroRNAs(miRs)serve a vital role in cancer progression.Extensive research has revealed that miR-26 a is abnormally expressed and functions as a tumor suppressor in numerous cancer types.Thus,the present study aimed to examine the alterations in miR-26 a expression in breast cancer cells,as well as the effect on the growth,clone formation,migration,invasion and docetaxel sensitivity of human breast cancer cells.Furthermore,the potential mechanism of action of miR-26 a in breast cancer was explored.Methods: The clinical tissue specimens were gained from 13 breast cancer patients during surgery at The First Affiliated Hospital of University of Science and Technology of China.Reverse transcription-quantitative PCR was conducted to assess the differences in miR-26 a expression between human breast cancer and normal breast specimens.At the same time,the expression of miR-26 a in human breast cancer cell lines(SK-BR-3,BT474,MDA-MB-231,MDA-MB-468 and MCF-7)and the non-tumorigenic epithelial cell line MCF-10 A was tested.We verified whether miRNA-26 a affected cell proliferation and the number of colonies by the Cell Counting Kit-8 assays and cloning experiments.We performed the migration and invasion assays to evaluate cell metastasis.Bioinformatics analysis(Target Scan algorithm)was utilized to identify the putative target of miR-26 a.A luciferase activity experiment was utilized to validate the relationship between miR-26 a and family with sequence similarity 98 member A(FAM98A).We examined the differential expression of FAM98 A and Hedgehog signaling pathway associated proteins including sonic hedgehog signaling molecule(SHH),smoothened,frizzled class receptor(SMO)and glioma-associated oncogene homolog 1(GLI1)in miR-26 a mimic-transfected cells and miR-NC-transfected cells by western blot analysis.Results: The present results indicated that the relative m RNA expression level of miR-26 a was lower in breast cancer tissues than that in the adjacent non-cancerous tissues.MiR-26 a expression was upregulated in the MCF-10 A cells and was downregulated in breast carcinoma cell lines.The transfection of miR-26 a mimic significantly increased miR-26 a expression compared with that observed in the miR-NC group.Overexpression of miR-26 a significantly suppressed cell proliferation,cloning and sensitized breast cancer cells to docetaxel.Moreover,the migration and invasion of miR-26 a mimic-transfected cells were markedly suppressed compared with that of the miR-NC group.Bioinformatics analysis predicted the target binding sites of miR-26 a in FAM98 A 3’-UTR.A luciferase reporter assay suggested that miR-26 a directly targeted FAM98 A,and that the transfection of miR-26 a mimics sufficiently down-regulated FAM98 A,SHH,SMO and GLI1 expression levels.Conclusion: MiR-26 a negatively regulates the expression of FAM98 A,which could provide significant implications for the suppression of breast cancer carcinogenesis and development and enhancing docetaxel sensitivity of human breast cancer cells.