Identification of miR-146a is Associated with the Aggressiveness and Suppresses Proliferation via Targeting CDKN2A in Breast Cancer

Abstract

There is emerging evidence that some microRNAs can promote or suppress several human cancer development and progression. However, the profile and molecular mechanism of microRNAs for human breast cancer is poorly unknown. We used bioinformatics approaches to find new candidate diagnostic and therapeutic miRNAs in human breast cancer via analysis of TCGA RNA sequencing data and publicly GEO microarray data, in order to provide theoretical basis for the future investigations of breast cancer. Decreased expression miR-146a was identified as a key regulator of human breast cancer development and progression. Interestingly, we founded that miR-146a expression levels dependent on tumor size and pathological grading in breast cancer patients, but not associated with other factors including age, T classification. Kaplan-Meier survival analysis showed that patients with high miR-146a expression had a longer survival rate than those low miR-146a expressions. In vitro assays of over-expression miR-146a induces cell cycle arrest and inhibits MDA-MB-231 cell proliferation. Furthermore, luciferase reporter gene assays demonstrated that miR-146a directly combine the 3-untranslated region of CDKN2A mRNA. In conclusion, we demonstrated miR-146a play an important role in breast cancer development and progression.