MiR-185-5p Protects Against Angiogenesis in Polycystic Ovary Syndrome by Targeting VEGFA

Abstract

Polycystic Ovary Syndrome (PCOS) is a heterogeneous endocrine disease with high incidences in women of reproductive age. Although miR-185-5p (miR-185) was decreased in PCOS patients, the exact function of miR-185 on PCOS development still requires further investigation. In this study, rat injected with dehydroepiandrosterone (DHEA) was established as a PCOS model. A lentivirus carrying miR-185 was employed to examine its effect on PCOS symptoms. Then we performed the luciferase reporter assay to validate the interactions between miR-185 and vascular endothelial growth factor A (VEGFA). Finally, human ovarian microvascular endothelial cells (HOMECs) were induced by VEGF to explore the role of miR-185 in the angiogenic process. The results showed that miR-185 overexpression improved insulin level alteration and ovarian histological lesion in PCOS rats. We also found that miR-185 reduced the excessive angiogenesis as indicated by alterations of VEGFA, ANGPT1/2, PDGFB/D, a-SMA and CD31 in the ovary of PCOS rats. Luciferase reporter assay identified that VEGFA directly interacted with miR-185, and its expression level was negatively regulated by miR-185. The in vitro results further demonstrated that miR-185-induced suppression of cell proliferation, migration and tube formation was attenuated by VEGF in HOMECs. In summary, this is the first study to show that miR-185 can target VEGFA to inhibit angiogenesis, thus improving the development of PCOS. These findings develop a molecular candidate for PCOS prevention and therapy.

Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs

“…Given that hsa-miR-103a-3p responded to hypoxia and targeted argonaute 1 (AGO1) to promote angiogenesis ( Chen et al, 2013 ), and EXO-miR-103a increases angiogenesis in gastric cancer targeting c-MYB ( Liang et al, 2015 ), downregulation of exosomal hsa-miR-103a-3p in the BPD group is likely to suppress fetal angiogenesis. Our finding that hsa-miR-185-5p overexpression promotes angiogenesis is inconsistent with the previous report, which demonstrates that miR-185-5p suppresses the expression of vascular endothelial growth factor A (VEGFA), inhibiting angiogenesis in human ovarian microvascular endothelial cells ( Wei and Zhao, 2020 ). In our study, hsa-miR-185-5p overexpression did not significantly change VEGFA mRNA expression in HUVECs.…”

Exosomal Transfer of miR-185 Is Controlled by hnRNPA2B1 and Impairs Re-endothelialization After Vascular Injury

“…Previous studies have reported that miR-185-5p was a key regulator of angiogenesis through targeting cathepsin K (CatK), which plays an important role in regulating vascular repair (Li et al, 2019). Wei and Zhao (2020) reported that miR-185 inhibits angiogenesis in human ovarian microvascular endothelial cells by downregulating the level of VEGFA (Wei and Zhao, 2020). In this study, the supernatant from VSMCs was confirmed to contain exosomes that expressed miR-185.…”

MicroRNAs Targeting HIF-2α, VEGFR1 and/or VEGFR2 as Potential Predictive Biomarkers for VEGFR Tyrosine Kinase and HIF-2α Inhibitors in Metastatic Clear-Cell Renal Cell Carcinoma

“…The anti-angiogenic effect of miR-185-5p has been demonstrated in prostate cancer cells, in which it led to suppression of tumor development [ 46 ]. Its inhibition of angiogenesis has also been described in benign diseases such as polycystic ovarian syndrome through targeting of VEGFA [ 47 ]. In endometriosis, a disease characterized by increased angiogenesis, miR-185-5p is downregulated in plasma samples [ 48 ].…”