The miR-410-5p /ITGA6 axis participates in the pathogenesis of recurrent abortion by regulating the biological function of trophoblast

滋养层 转染 蛋白激酶B 细胞凋亡 基因敲除 细胞生物学 化学 PI3K/AKT/mTOR通路 细胞生长 信号转导 细胞培养 癌症研究 胎盘 生物 胎儿 生物化学 遗传学 怀孕
作者
Shujuan Wu,Huifan Liu,Mengqi Zhou,Ye Shang,Lingbo Luo,Jiao Chen,Jing Yang
出处
期刊:Journal of Reproductive Immunology [Elsevier]
卷期号:152: 103647-103647 被引量:12
标识
DOI:10.1016/j.jri.2022.103647
摘要

The purpose of this study was to determine the regulation of the miR-410-5p /ITGA6 axis on the biological functions of trophoblast cells and the mechanism involved in recurrent spontaneous abortion(RSA). We used qRT-PCR and Western blotting to quantify the expression levels of Mir-410-5p and ITGA6 in placenta of RSA and normal, and found that compared with normal placenta, the placenta of RSA patients showed higher miR-410-5p and lower ITGA6 expression. Dual luciferase reporter gene assay confirmed the binding of miR-410-5p to ITGA6. The expression of miR-410-5p and ITGA6, and proliferation, apoptosis, invasion and migration of trophoblast cells and the effect on the polarization of M2 macrophages were detected in the trophoblast derived cell lines HTR8/Svneo transfected with miR-410-5p mimic, sh-miR-410-5p and si-ITGA6 respectively. Meanwhile, the molecular mechanism of ITGA6 regulation on trophoblast cells was explored. Transfection with miR-410-5p mimic or si-ITGA6 attenuated the proliferation, migration and invasion and induced apoptosis of HTR-8/SVneo cells. Transfection of sh-miR-410-5p promoted proliferation, migration and invasion, and weakened apoptosis of HTR-8/SVneo cells. In addition, overexpression of miR-410-5p in trophoblast cells inhibited the polarization of M2 macrophages, while knockdown of miR-410-5p was beneficial to recruitment of trophoblast cell and promoted the polarization of M2 macrophages. ITGA6 may affect the biological functions of trophoblast cells by regulating PI3K/AKT and MAPK signaling pathways. In conclusion, miR-410-5p mediates trophoblast cell proliferation, apoptosis, invasion and migration through regulating ITGA6 expression.
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