MiR-143-3p facilitates motility and invasiveness of endometriotic stromal cells by targeting VASH1/TGF-β signaling

Abstract

Endometriosis is a benign gynecological disease. Accumulating evidence has revealed the participation of dysregulated miRNAs in the progression of endometriosis. Here, the function and molecular mechanism of miR-143-3p in endometriosis were investigated. The levels of vasohibin 1 (VASH1) and miR-143-3p in endometrial tissues and endometriotic stromal cells (ESCs) were detected by RT-qPCR. Migrative and invasive phenotypes of ESCs were tested by Transwell assays. The protein expression of VASH1, TGF-β signaling markers, and epithelial to mesenchymal transition (EMT) markers was examined by western blotting. The targeted relationship between miR-143-3p and VASH1 was confirmed by bioinformatics analysis and luciferase reporter assay. We found that miR-143-3p expression was significantly upregulated in ectopic endometrial tissues compared to that in eutopic and normal endometrial tissues. MiR-143-3p knockdown restrained EMT process, invasive and migrative behaviors of ESCs. Mechanically, miR-143-3p targeted VASH1 and negatively regulated VASH1. VASH1 downregulation reserved the effects of miR-143-3p knockdown in ESCs. MiR-143-3p activated TGF-β signaling via targeting VASH1. Furthermore, activation of TGF-β signaling counteracted the miR-143-3p knockdown-caused suppression of migration, invasion and EMT process in ESCs. Overall, miR-143-3p activates TGF-β signaling by targeting VASH1 to facilitate migration and invasion of ESCs.

Keywords: Endometriosis; VASH1; miR-143-3p.