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

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

  • J Reprod Immunol. 2022 Aug;152:103647. doi: 10.1016/j.jri.2022.103647.
Shujuan Wu 1 Huifan Liu 2 Mengqi Zhou 1 Ye Shang 1 Lingbo Luo 1 Jiao Chen 3 Jing Yang 4
Affiliations

Affiliations

  • 1 Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei, China.
  • 2 Department of Spine Surgery & Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
  • 3 Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei, China. Electronic address: [email protected].
  • 4 Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei, China. Electronic address: [email protected].
Abstract

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.

Keywords

Biological function; ITGA6; Macrophages; MiR-410-5p; Trophoblast cells.

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