Abstract
Background: 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.Methods: 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 breast cancer’s malignant phenotype. Related proteins expression in MEK/MAPK pathway was determined by western blot analysis. Results: PRNCR1 was abnormally highly expressed and miR-377 was poorly expressed in 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 may participate in the modulation of CCND2 by competitively binding with 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.Conclusion: Our study highlights that lncRNA PRNCR1 may competitively bind to miR-377, leading to upregulated CCND2, which in turn leads to MEK/MAPK pathway activation, thereby promoting breast cancer growth.
Hypoxic Breast Cancer Cell-Derived Exosomal SNHG1 Promotes Breast Cancer Growth and Angiogenesis via Regulating miR-216b-5p/JAK2 Axis
