MiR-181a-5p Promotes Anoikis During Detachment Induction In The Mammary Epithelial Cell Line MCF10A

Anoikis is induced by detachment of mammary epithelial cells from the extracellular matrix(ECM). Tumor metastasis is the main cause of death in cancer patients. As an early barrier for metastasis, anoikis is a critical mechanism in maintaining tissue homeostasis and development. Anoikis resistance facilitates tumorigenesis and metastasis.MicroRNAs(miRNA) are a class of 21-22 nt short noncoding RNA that can regulate gene expression by binding to their target mRNA. The relatively recent discovery of microRNAs as novel and potent modulators in a diverse range of cellular pathways has opened a door for the understanding and treatment of human disease. In this study, we selected a dozen of miRNAs regualting autophagy and detected the change of these miRNAs′ expression during anoikis. We found that the expression of miR-181a-5p, miR-30 b and miR-338-5p was increased significantly. Moreover, miR-181a-5p was found to attenuate anoikis resistance in the mammary epithelial cell line MCF10 A. Interestingly, miR-181a-5p was also found to repress autophagy, an important survival mechanism during anoikis. Simultaneously, the expression level of ATG5, a target gene of miR-181a-5p, decreased significantly. Furthermore, overexpression of ATG5 in mi R-181a-5p stably transfected MCF10 A cells reversed the effects of miR-181a-5p on anoikis.Taken together,these results suggested that miR-181a-5p could attenuate anoikis resistance through inhibiting autophagy by targeting ATG5. The expected results may help to develop a novel therapeutic strategy for cancer.