Effect of miR-182 regulating HIF-2α pathway on hypoxia-induced invasion of preeclampsia trophoblasts

Acta Universitatis Medicinalis Anhui 2020 06 v.55 876-881     font:big middle small

Found programs:

Authors:Yang Juan; Xie Yingying

Keywords:miR-182;hypoxia-inducible factor 2α;cell invasion

DOI:10.19405/j.cnki.issn1000-1492.2020.06.011

〔Abstract〕 Objective To investigate the effects of miR-182 and hypoxia inducible factor-2α(HIF-2α) pathway on the invasion of human extravillous trophoblasts(HTR8/SVneo) during early pregnancy induced by hypoxia. Methods 67 pre-eclampsia(PE) pregnant women were selected as the study subjects, and 84 healthy pregnant women were selected as the control group. All of them underwent cesarean section voluntarily, and placental tissues were collected after operation. HTR8/SVneo cells were culturedin vitroand transfected with miR-182 inhibitor. They were divided into control group, hypoxia group, miR-182 inhibitor group and miR-182 inhibitor negative control group. The expression levels of HIF-2α, vascular endothelial growth factor(VEGF)in placental tissues and HIF-2α, VEGF, E-cadherin, matrix metalloproteinase 9(MMP-9) and MMP-2 in HTR8/SVneo cells were determined by Western blot.The expression of miR-182 in placental tissues and HTR8/SVneo cells was detected by real-time fluorescence quantitative assay(RT-qPCR). Cell apoptosis was detected by flow cytometry, and the invasive ability of cells was determined by Transwell invasion assay in each group. Results Compared with the control group, the expression of HIF-2α and VEGF in placenta of PE patients increased significantly, while the expression of miR-182 decreased significantly(P<0.05). Compared with the control group, the apoptotic rate of hypoxia group increased significantly, the expression levels of invasive ability, miR-182, MMP-9 and MMP-2 decreased significantly, and the expression levels of E-cadherin, HIF-2α and VEGF increased significantly(P<0.05). Compared with the hypoxic group and the miR-182 negative control group, the apoptotic rate of the miR-182 inhibitor group was significantly lower, the invasive ability was significantly higher, the expression levels of HIF-2α, VEGF, MMP-9 and MMP-2 were significantly higher, and the expression levels of miR-182 and E-cadherin were significantly lower(P<0.05). TargetScan database predicted that HIF-2α was the target gene of miR-182, and double luciferase assay confirmed that HIF-2α was the target of miR-182. Conclusion The expression of miR-182 in placenta of PE patients is low, HIF-2α is highly expressed, and miR-182 may enhance the invasive ability of trophoblasts under hypoxia by activating HIF-2α/VEGF signaling pathway.