MicroRNA-205-5p inhibits the growth and migration of breast cancer through targeting Wnt/β-catenin co-receptor LRP6 and interacting with lncRNAs.

Abstract

Breast cancer is the most prevalent type of cancer among women worldwide. Non-coding RNAs play a fundamental role in regulating the expression of different genes. MicroRNAs (miRNAs) are known to bind to mRNA and either induce its degradation or repress its translation. Also, miRNA can modulate the expression of long non-coding RNAs (lncRNA) through different mechanisms. This study aims to determine the role of miRNA-205-5p in breast cancer cell lines. miR-205-5p was bioinformatically predicted to interact with LRP6 mRNA and lncRNAs MALAT1, NEAT1, SNHG5, and SNHG16. Then, the levels of miR-205-5p and its target genes and lncRNAs in breast cancer cell lines MCF-7 and MDA-MB-231 were determined. In addition, MCF-7 and MDA-MB-231 breast cancer cells were transfected with miR-205-5p mimic or miRNA mimic negative control using lipofectamine 3000, and the effect of miR-205-5p overexpression on cellular proliferation and migration was assessed. Moreover, we probed the impact of miR-205-5p overexpression on the expression levels of LRP6, Wnt/β-catenin pathway genes, lncRNAs, and apoptotic markers. miR-205-5p upregulation resulted in decreasing the growth and migration and induced apoptosis markers in the two tested breast cancer subtypes. Additionally, miR-205-5p overexpression resulted in decreasing the expression of LRP6 in MCF-7 and MDA-MB-231 cells leading to downregulation of Wnt/β-catenin target genes, c-Myc, cyclin D1, and PPARδ and had various regulatory effects on the expression of lncRNAs MALAT1, NEAT1, SNHG5, and SNHG16. miR-205-5p inhibits the proliferation and migration of breast cancer through diverse mechanisms including targeting LRP6, Wnt/β-catenin pathway, and its regulatory effects on lncRNAs.