Progesterone ameliorates the endometrial polyp by modulating the signaling pathway of Wnt and β-catenin via regulating the expression of H19 and miR-152.

Abstract

MicroRNAs and long noncoding RNAs are believed to play important roles in the pathogenesis of various diseases. This study aimed to explore the potential mechanism of the involvement of H19 and miR-152 in an endometrial polyp. Luciferase assay was conducted to determine the effect of progesterone. Real-time polymerase chain reaction (PCR) and western blot were performed to detect the influence of progesterone on miR-152 and Wnt1. MTT assay and flow cytometry (FCM) were utilized to detect the effect of progesterone on cell proliferation and apoptosis. In silicon analysis, luciferase assay, real-time PCR, and immunohistochemistry (IHC) were performed to explore the regulatory relationship between H19 and miR-152 or miR-152 and Wnt1. Progesterone dose-dependently increased the H19 expression level through driving the promoter efficiency of H19. Then, progesterone upregulated Wnt1 level and downregulated miR-152 in a dose-dependent manner in ECC1 and HEC1A cells. Administration of progesterone inhibited cell viability and promoted cell apoptosis. H19 negatively regulated miR-152 expression by binding to miR-152. Furthermore, Wnt1 was identified as a virtual target gene of miR-152 and was inhibited by miR-152. Progesterone receptors mRNA and miR-152 were lowly expressed in participants with an endometrial polyp, while the levels of H19 and Wnt1 were much higher in the endometrial polyp group compared with normal controls. H19 negatively regulated miR-152 and miR-152 negatively regulated Wnt1, with the negative correlation coefficients being -0.500 and -0.500, respectively. Using IHC, it was found that Wnt1 and Bcl-2 protein were highly expressed in the endometrial polyp group compared with normal controls. The results suggested that H19 was associated with endometrial polyp via mediating cell proliferation and apoptosis.