Overexpression of let-7b exerts beneficial effects on the functions of human placental trophoblasts by activating the ERK1/2 signaling pathway
Overexpression of let-7b exerts beneficial effects on the functions of human placental trophoblasts by activating the ERK1/2 signaling pathway
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DOI：
10.1002/mrd.23535
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发表时间：
2021-09-22
影响因子：
2.5
通讯作者：
Meng, Tao
中科院分区：
文献类型：
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作者：
Gao, Yanyan;Zhang, Xuefeng;Meng, Tao
本研究旨在探讨let-7 b调控胎盘滋养细胞功能的分子机制，并检测胎盘let-7 b在子痫前期（PE）中的表达。人滋养层HTR-8/SVneo细胞分别用对照和过表达let-7 b的慢病毒转导。细胞增殖评估使用细胞计数试剂盒-8（CCK-8）和5-乙炔基-2 '-脱氧尿苷（EdU）测定。细胞凋亡，自噬，炎症，上皮间质转化（EMT），和ERK 1/2信号相关蛋白进行了评估免疫印迹。胎盘组织样品收集自正常妊娠妇女（n = 20）和PE患者（n = 14）。Let-7 b在HTR-8/SVneo细胞中的过表达显著诱导细胞增殖和侵袭，抑制细胞凋亡和自噬，并导致滋养层细胞中肿瘤坏死因子α（TNF-α）表达降低和白细胞介素6（IL-6）表达增加。值得注意的是，let-7 b过表达的有益作用，包括细胞侵袭和EMT，在很大程度上被U 0126（一种间接ERK 1/2信号传导抑制剂）逆转。TGF-β 1型受体（TGF-β receptor type-1，TGFBR 1）过表达减弱了let-7 b在ERK通路激活和滋养细胞侵袭中的作用。与正常对照组相比，PE病例的胎盘组织标本显示let-7 b表达显著降低。let-7 b的过表达通过ERK 1/2信号通路对人胎盘滋养层细胞的功能产生有益的影响，并且在人PE中胎盘let-7 b被下调。这些发现表明let-7 b是PE前瞻性诊断和靶向治疗的有希望的生物标志物。
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 factor alpha (TNF-alpha) 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-beta 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.