Background
The cross-talk between RNA binding proteins (RBPs) and microRNAs (miRNAs) in the regulation of gene expression is a complex process. Here, we describe a new mode of regulation of TRIM25 expression mediated by an antagonistic interplay between IGF2BP3 and miR-3614-3p.
Methods
The expression level of TRIM25, IGF2BP3, pri-miR-3614 and miR-3614-3p in breast cancer (BC) tissues, non-tumor tissues and BC cell lines were detected by qRT-PCR, Western blot and Immunohistochemistry (IHC). Binding of miR-3614-3p and IGF2BP3 to TRIM25 RNA was verified using luciferase activation assays, RNA immunoprecipitation (RIP) and biotin pull-down assays. In vitro and in vivo loss- and gain-of-function studies were performed to reveal the effects and related mechanism of IGF2BP3-miR-3614-3p-TRIM25 axis in in breast cancer cells proliferation. Findings: We found that an intragenic miRNA-3614-3p inhibits the expression of its host gene TRIM25 by binding to its 3'- untranslated region (UTR). Interestingly, IGF2BP3 can competitively occupy this binding site and inhibit miRNA-3614 maturation, thereby protecting TRIM25 mRNA from miR-3614-mediated degradation. The overexpression of miR-3614-3p dramatically inhibited breast cancer cell growth through the downregulation of TRIM25. Furthermore, the silencing of IGF2BP3 reduced TRIM25 expression, suppressed cell proliferation, and exhibited a synergistic effect with miR-3614-3p overexpression. Interpretation: Collectively, these