LncRNA PRNCR1 Promotes Breast Cancer Proliferation and Inhibits Apoptosis by Modulating microRNA-377/CCND2/MEK/MAPK Axis

Abstract

Long non-coding RNAs (lncRNAs) have recently become the vital gene regulators in diverse cancers. In our study, we purposed to inquiry into the mechanisms of lncRNA PRNCR1 in breast cancer via microRNA-377 (miR-377)/CCND2/MEK/MAPK axis. PRNCR1 expression in breast cancer tissues was detected, and the correlation between PRNCR1 expression and prognostic survival was analyzed. The expressions of PRNCR1 and miR-377 in breast cancer cell lines were detected. Relationships among PRNCR1, miR-377 and CCND2 were confirmed by luciferase activity, RNA pull-down or RIP assays. Breast cancer cells were introduced with silenced PRNCR1 or restored miR-377 to explore their functions in malignant phenotype of breast cancer cells. The expression of MEK/MAPK pathway-related proteins was determined by western blot analysis. PRNCR1 was highly expressed and miR-377 was poorly expressed in patients with breast cancer, and patients with high expression of PRNCR1 had a poor prognosis. PRNCR1 silencing or miR-377 overexpression resulted in suppressed breast cancer cell proliferation ability, blocked cell cycle process and induced apoptosis. PRNCR1 regulated CCND2 expression by competitively binding to miR-377. CCND2 activated the MEK/MAPK pathway, and after treatment with Mirdametinib, the MEK/MAPK pathway was inhibited, which was found to retard breast cancer growth. Our study highlights that lncRNA PRNCR1 may competitively bind to miR-377, leading to upregulated CCND2, which in turn activated MEK/MAPK pathway to promote breast cancer growth.