MicroRNA-16 inhibits endometrial stromal cell migration and invasion through suppression of the inhibitor of nuclear factor-κB kinase subunit β/nuclear factor-κB pathway

Abstract

Accumulating evidence has demonstrated that endometrial stromal cells (EScs) are responsible for the pathogenesis of endometriosis (Ems), which is characterized by the presence of functional endometrial-like tissues outside the uterine cavity. Abnormal expression of microRNAs (miRNAs) in EScs may be implicated in the etiology of Ems; however, the exact mechanisms have yet to be fully elucidated. The aim of the present study was to investigate the effects of miRNAs on EScs and the underlying mechanisms. Using a microarray assay, microRNA-16 (miR-16) was found to be significantly downregulated in the ectopic endometrial tissues in patients with Ems, compared with that in eutopic endometrial tissues. Overexpression of miR-16 significantly suppressed the migration and invasion of EScs, whereas miR-16 inhibition exerted the opposite effects. Furthermore, dual luciferase reporter assay demonstrated that miR-16 directly targeted the inhibitor of nuclear factor (NF)-κB kinase subunit β (IKKβ) and suppressed its translation. It was observed that the expression of IKKβ was upregulated and inversely correlated with miR-16 levels in the ectopic endometrial tissues in patients with Ems. Additionally, knockdown of IKKβ by si-IKKβ mimicked the effects of miR-16 overexpression on EScs, while the promoting effects of IKKβ overexpression on the migration and invasion of EScs were attenuated by miR-16 overexpression. Finally, miR-16 inhibited the activation of the NF-κB pathway by targeting IKKβ. collectively, these results demonstrated that miR-16 may suppress Ems by inhibiting the IKKβ/NF-κB pathway, suggesting that miR-16 may be a useful target in the treatment of Ems.