MiR-641 Inhibited Cell Proliferation and Induced Apoptosis by Targeting NUCKS1/PI3K/AKT Signaling Pathway in Breast Cancer.

Abstract

Objective Studies revealed an important role of microRNAs (miRNAs) in multiple cancers, including breast cancer. In the present study, we evaluated the role and function of miR-641 in breast cancer. Methods The expression level of miR-641 in breast cancer cell lines (Hs-578T, MCF7, HCC1937, and MAD-MB-231) was determined by real-time PCR. Functional analyses, including CCK-8 assay, transwell assay, wound-healing assay, and apoptosis detection, were carried out to explore the roles of miRNA-641 in malignant behaviors of breast cancer. Luciferase report assay was used to investigate the regulatory association of miRNA-641 with its potential targets. Results The expression levels of miR-641 were downregulated, while the expression levels of nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) were increased in breast cancer cell lines. The in vitro results showed that miR-641 repressed proliferation and migration/invasion and promoted apoptosis of breast cancer cells. NUCKS1, a positive regulator of phosphatidylinositol-3-kinases (PI3K)/protein-serine-threonine kinase (AKT) pathway, was confirmed as a direct target of miR-641. The of treatment of the PI3K agonist, 740Y-P, could abrogate the antioncogenic potentials of miR-641 in breast cancer cells. Conclusion miR-641 functioned as a tumor suppressor through the PI3K/AKT signaling pathway via targeting NUCKS1 in breast cancer.