Overexpression of let‐7b exerts beneficial effects on the functions of human placental trophoblasts by activating the ERK1/2 signaling pathway

Abstract

The present work aimed to explore let-7b's molecular mechanisms that regulate the functions of placental trophoblasts and to examine placental let-7b expression in human pre-eclampsia (PE). Human trophoblast HTR-8/SVneo cells underwent transduction with control and let-7b overexpressing lentiviruses, respectively. Cell proliferation assessment utilized cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays. Apoptosis, autophagy, inflammation, epithelial-to-mesenchymal transition (EMT), and ERK1/2 signaling-associated proteins were assessed by immunoblot. Placental tissue samples were collected from women with normal pregnancy (n = 20) and PE patients (n = 14). Let-7b overexpression in HTR-8/SVneo cells remarkably induced cell proliferation and invasion, suppressed apoptosis and autophagy, and resulted in decreased tumor necrosis factorα (TNF-α) expression and increased interleukin 6 (IL-6) expression in trophoblasts. Notably, the beneficial effects of let-7b overexpression, including cell invasion and EMT, were largely reversed by treatment with U0126, an indirect ERK1/2 signaling inhibitor, in these cells. TGF-β receptor type-1 (TGFBR1) overexpression weakened let-7b's functions in ERK pathway activation and invasion in trophoblasts. Placental tissue specimens from PE cases demonstrated significantly lower let-7b expression compared with normal controls. Overexpression of let-7b exerts beneficial effects on the functions of human placental trophoblasts via ERK1/2 signaling, and placental let-7b is downregulated in human PE. These findings suggest let-7b is a promising biomarker for the prospective diagnosis and targeted therapy of PE.

Role of microRNAs regulating trophoblast cell function in the pathogenesis of pre‑eclampsia (Review)

“…In addition, expression of let-7b is significantly decreased in the placenta of patients with PE. Let-7b adversely affects the function of trophoblasts via the ERK1/2 signalling pathway and it inhibits cell proliferation and invasion, promotes cell apoptosis and autophagy, as well as increasing TNF-α expression in trophoblasts of patients with PE ( 43 ). On the other hand, miR-134 inhibits infiltration of trophoblasts by targeting ITGB1( 44 ).…”

The Metabolism Reprogramming of microRNA Let-7-Mediated Glycolysis Contributes to Autophagy and Tumor Progression

“…The Let-7b -mediated TGFBR1/ERK/IL-6/TNF-α cascade triggers not only apoptosis but also autophagy. Such regulation may contribute to pre-eclampsia during pregnancy [ 90 ]. In glioma, the downregulation of STAT3 was mediated by Let-7a , Let-7d , and Let-7f .…”