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

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.