miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis

Abstract

It is believed that endometrial miRNAs contribute to the aetiology of endometriosis in stem cells; however, the mechanisms remain unclear. Here we collected serum samples from patients with or without endometriosis and characterized the miRNA expression profiles of these two groups. MicroRNA-199a-5p (miR-199a-5p) was dramatically down-regulated in patients with endometriosis compared with control patients. In addition, we found that the tumour suppressor gene, SMAD4, could elevate miR-199a-5p expression in ectopic endometrial mesenchymal stem cells. Up-regulation of miR-199a-5p suppressed cell proliferation, motility and angiogenesis of these ectopic stem cells by targeting the 3' untranslated region of VEGFA. Furthermore, we established an animal model of endometriosis and found that miR-199a-5p could decrease the size of endometriotic lesions in vivo. Taken together, this newly identified miR-199a-5p module provides a new avenue to the understanding of the processes of endometriosis development, especially proliferation, motility and angiogenesis, and may facilitate the development of potential therapeutics against endometriosis.

Circulating miR-200–family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time

“…However, each study found a different set of possible markers (14)(15)(16)(17)(18), with miR-199a being the only marker reported twice (16,17). Still, the direction of alteration in miR-199a levels among patients was opposite the alterations in these reports.…”

“…Recent studies have focused on different proteomic, transcriptomic, and metabolomic approaches for discovering endometriosis biomarkers (11), and during the past few years miRNAs have emerged as novel candidate markers for the disease. Several potential circulating blood miRNA biomarkers for endometriosis have already been proposed (14)(15)(16)(17)(18), but the results are inconsistent and no single miRNA alteration has been confirmed by other studies.…”

MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

“…Bevacizumab, a specific anti-VEGF drug that has led to over survival times of about 24 months when combined with standard chemotherapy regimens compared with about 20 months when treated with standard chemotherapy alone [29,30]. Some VEGFA-targeted miRNAs including miR-203 [31], miR-497 [32], miR-26a [33], and miR-199a-5p [34] have According to several algorithms, we predicted that miR-140-5p may directly target VEGFA. Using a dual-luciferase reporter assay we showed that miR-140-5p directly bound to the 3'UTR of VEGFA, which contains a miR-140-bingding site.…”

Genome-Wide Microarray Analysis of Long Non-Coding RNAs in Eutopic Secretory Endometrium with Endometriosis

“…Therefore, CDC6 might be one of the candidate genes of endometriosis and its action might be related to the theory of epithelial-mesenchymal transition. A biology prediction method found CDC6 and the miReutopic and ectopic endometrium of women with endometriosis [42]. MiRNAs can regulate the expression of lncRNA negatively or positively [43] LINC00313 is a kind of lncRNA.…”