MiR-101 regulates apoptosis of trophoblast HTR-8/SVneo cells by targeting endoplasmic reticulum (ER) protein 44 during preeclampsia

Abstract

To investigate a possible association between miR-101 and apoptosis of human trophoblast cells mediated by endoplasmic reticulum protein 44 (ERp44) in preeclampsia (PE), we explored the expression of miR-101 in PE placentas (n=30) compared with normotensive pregnant placentas (n=30) and the correlation between miR-101 and ERp44 was also analyzed. Furthermore, both the apoptotic rate of trophoblast cells and the ER stress-induced apoptotic proteins were assayed when the HTR-8/SVneo cells were treated with miR-101 mimics or inhibitors in vitro. We found a lower expression of miR-101 and an inverse correlation between miR-101 and ERp44 protein in PE placentas. Upregulation of miR-101 expression could inhibit trophoblast HTR-8/SVneo cell apoptosis and repress ER stress-induced apoptotic proteins by targeting ERp44 in vitro, whereas inhibition of miR-101 could induce HTR-8/SVneo cell apoptosis. Our findings indicated that overexpression of miR-101 could downregulate ERp44 and suppress apoptosis in trophoblast cells during PE. Therefore, loss of miR-101 expression could contribute to ER stress-induced trophoblast cell apoptosis by targeting ERp44.

MicroRNA-101 protects cardiac fibroblasts from hypoxia-induced apoptosis via inhibition of the TGF-β signaling pathway

“…In addition, a study by Wang et al (2014) demonstrated that miR-101 induced apoptosis in breast cancer cells by targeting Janus Kinase 2. However, Zou et al (2014) found that miR-101 suppressed stressinduced trophoblast apoptosis by targeting ERp44. Additionally, a recent study (Tu et al, 2014) reported that miR-101 significantly attenuated TGF␤1-induced hepatocyte apoptosis.…”

MicroRNAs: crucial regulators of placental development

“…Overexpression of miR-18a increased apoptosis by inducing the expression of estrogen receptor alpha (ESR1) (Zhu et al 2015), while miR-128a induced apoptosis via the mitochondrial pathway by downregulating BAX (Ding et al 2016) and miR-30a-3p by inhibiting IGF1 (Niu et al 2018). On the other hand, miR-101 targeted endoplasmic reticulum protein 44 (ERP44) to suppress ER-stress-induced apoptosis (Zou et al 2014). Again, as majority of these studies were carried out using only cell lines, more studies are required to confirm the involvement of these miRNAs in trophoblast cell proliferation and apoptosis.…”

Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications

“…For example, overexpression of miR-378a-5p and miR-376c enhanced these processes [77, 78]. So far, only a handful of miRNAs, including miR-424 [79], miR-101 [52], miR-18a [46], miR-335 [50], miR-137 [55], and miR-155 [61], have been implicated in trophoblast dysfunction through various targets, including endothelial nitric oxide synthase (eNOS) and soluble vascular endothelial growth factor receptor 1 (sVEGFR-1 or sFlt-1).…”