hsa-miR-199a-3p Inhibits Motility, Invasiveness, and Contractility of Ovarian Endometriotic Stromal Cells.

It is suggested that aberrantly expressed microRNAs are involved in the pathogenesis of endometriosis. Our previous study demonstrated that expression of the microRNA hsa-miR-199a-3p is attenuated in human endometriotic cyst stromal cells (ECSCs). The current study aimed to define the roles of hsa-miR-199a-3p in the development of endometriosis. ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometrioma and normal endometrial tissues, respectively. We evaluated the effect of transfected hsa-miR-199a-3p on the migration, invasion, and contractility of ECSCs using Transwell migration assays, in vitro wound healing assays, Transwell invasion assays, and collagen gel contraction assays. We also examined the downstream target of hsa-miR-199a-3p with an online public database search and luciferase reporter assay. Expression of hsa-miR-199a-3p in ECSCs was significantly lower than that in NESCs, whereas the expression of p21-activated kinase 4 (PAK4) mRNA was significantly higher. Transfection of hsa-miR-199a-3p inhibited the migration, invasion, and contractility of ECSCs via inhibition of PAK4 mRNA expression. PAK4 was confirmed to be the direct target of hsa-miR-199a-3p. Transfection of PAK4 small interfering RNA and the PAK4 inhibitor PF-3758309 also inhibited ECSC migration, invasion, and contractility. These findings suggest that hsa-miR-199a-3p may act as a tumor suppressor in endometriosis development. Attenuation of hsa-miR-199a-3p expression was favorable for ECSCs to acquire the highly invasive, motile, and contractile characteristics of endometriotic cells and is involved in the development of endometriosis. Accordingly, PAK4 inhibitors may be promising for the treatment of endometriosis.