miR‐215‐5p decreases migration and invasion of trophoblast cells through regulating CDC6 in preeclampsia

Abstract

Preeclampsia (PE) is a serious disease that occurs after 20 weeks during pregnancy.There are some aberrant microRNAs (miRNAs) that are associated with the etiology of PE. As discovered by scholars, there was an increased level of miR-215-5p in plasma of PE patients compared with the control group; nonetheless, there is still no knowledge of the mechanism of miR-215-5p in PE. We carried out the comparison of the expression levels of miR-215-5p, and the supposed target gene cell division cycle 6 (CDC6) in 30 placentas from PE patients as well as 30 placentas from normal pregnant women. The verification of the impacts of miR-215-5p and CDC6 was carried out by functional assays in HTR-8/SVneo cells transfected with the miR-215-5p mimic or siR-CDC6. As indicated by findings, miR-215-5p showed an apparent increase; conversely, CDC6 was inhibited in the experiment group. The upregulation of miR-215-5p inhibited both the migration and invasive potential of trophoblasts, besides decreasing the G1-S transition and downregulating CDC6 in HTR-8/SVneo cells; nonetheless, it did not significantly impact the cell proliferation. Furthermore, siR-CDC6 replicated the functions of the miR-215-5p mimic. Also, the miR-215-5p mimic and siR-CDC6 both decreased the epithelial-mesenchymal transition (EMT) with additional E-cadherin level and decreased the expressions of N-cadherin as well as vimentin in trophoblast cells. To conclude, miR-215-5p decreased not only the migration but also the invasion of trophoblasts through regulating CDC6, which indicated that miR-215-5p might be associated with the etiology of PE.Significance of the study: More and more attention has been paid on the roles of miRNAs in the pathogenesis of PE. However, there is no study of miR-215-5p in the etiology of PE. We first investigated the mechanism of miR-215-5p in placental tissues and HTR-8/SVneo cells. It was suggested that miR-215-5p decreased the abilities of migration and invasion of trophoblasts through regulating CDC6 in PE. miR-215-5p might be used as an target for the early diagnosis and treatment of PE in the future. K E Y W O R D S preeclampsia, miR-215-5p, CDC6, EMT, placenta Abbreviations: CCK-8, Cell Counting Kit-8; CDC6, cell division cycle 6; cDNA, complementary DNA; DMEM, Dulbecco's modified Eagle's medium; EMT, epithelial-mesenchymal transition.; FBS, fetal bovine serum; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; miRNA, microRNA; PBS, phosphate-buffered saline solution; PE, preeclampsia; PI, propidium iodide; PVDF, polyvinylidene fluoride; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Silencing ZEB2 Induces Apoptosis and Reduces Viability in Glioblastoma Cell Lines

“…For instance, in an article, it was shown that miRNA-214-5p suppresses the aggressiveness of breast cancer cells through targeting Sox9 [56]. It was also shown that miR-214 inhibits the migration of trophoblast cells [57]. In an article by Gao et al, it was investigated that peroxisome proliferator-activated receptor α (PPARα) as a transcription factor and one of the nuclear hormone receptor superfamily members is dysregulated in various cancers including glioblastoma.…”

Wogonin Induces Apoptosis and Reverses Sunitinib Resistance of Renal Cell Carcinoma Cells via Inhibiting CDK4-RB Pathway

“…Researches have reported the role of CDC6 in EMT. CDC6 could regulate the expression of E- and N-Cadherin to affect the migration and invasion of trophoblast cells in preeclampsia ( Yang and Meng, 2020 ). Targeting CDC6 has also been shown to sensitized cancer cells to ionizing radiation-induced apoptosis, and reversed EMT ( Yu et al., 2019 ).…”

Roles of noncoding RNAs in preeclampsia

“… [ 108 ] miR-133 serum upregulated Rho/ROCK MiR-133 may affect the apoptosis of trophoblasts in the placenta tissues [ 109 ] miR-384 placenta/plasma upregulated PTBP3 Cell proliferation and migration were inhibited by miR-384 overexpression [ 110 ] miR-21 Serum/placenta upregulated FOXM1 MiR-21 may regulate placental cell proliferation [ 111 ] miR-125a-5p placenta/exosome upregulated VEGFA miR-125a-5p might affect HTR8/SVneo cell proliferation and migration and inhibit angiogenesis [ 112 ] miR-214-3p serum upregulated PIGF Downregulation of miR-214-3p promoted trophoblast invasion into the decidua, as well as spiral artery remodeling [ 113 ] miR-518b plasma upregulated EGR1 Increased miR-518b inhibited trophoblast migration and angiogenesis [ 114 ] miRNA-646 serum upregulated VEGF-A miR-646 suppressed endothelial progenitor cells (EPCs) multiplication, differentiation and migration. [ 115 ] miR-215-5p placenta upregulated CDC6 miR-215-5p inhibited both the migration and invasive potential of trophoblasts, besides decreasing the G1-S transition in HTR-8/SVneo cells [ 116 ] miR-483 venous blood/ umbilical cord blood / placental tissue downregulate IGF1 miR-483 regulates the expression of PI3K, Akt, and mTOR in endothelial progenitor cells [ 117 ] …”