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Silencing of LncRNA SNHG6 protects trophoblast cells through regulating miR-101-3p/OTUD3 axis in unexplained recurrent spontaneous abortion

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Abstract

Recurrent spontaneous abortion (RSA) is a gestational disease with complex pathogenesis, and trophoblast cells are closely involved in the pathogenesis of RSA. This study aimed to explore the regulatory effects and mechanisms of SNHG6 on trophoblast cells. The expression of SNHG6, miR-101-3p, and OTUD3 were detected in villous tissues from patients with unexplained RSA and normal pregnant women with induced abortion by qRT-PCR. The target relationships between miR-101-3p and SNHG6/OTUD3 were confirmed by dual-luciferase reporter assay. The viability, migration, and apoptosis of trophoblast cells were measured by MTT, wound healing, and flow cytometry assays, respectively. Western blot was performed to detect the protein expression of OTUD3, Ki-67, Bax, and Bcl-2. The results showed that SNHG6 and OTUD3 were up-regulated, and miR-101-3p was down-regulated in RSA patients. MiR-101-3p was a target of SNHG6, and OTUD3 was a target of miR-101-3p. There were negative correlations between the expression of miR-101-3p and OTUD3/SNHG6 in RSA patients. In addition, both SNHG6 silencing and miR-101-3p overexpression could increase cell viability and migration, decrease cell apoptosis, up-regulate Ki-67 and Bcl-2, and down-regulate Bax in HTR-8/SVneo cells. The effects of SNHG6 silencing on HTR-8/SVneo cells were reversed by miR-101-3p silencing or OTUD3 overexpression. To sum up, silencing of SNHG6 enhanced the viability and migration, and inhibited the apoptosis of trophoblast cells through regulating miR-101-3p/OTUD3. SNHG6/miR-101-3p/OTUD3 may be potential targets for the prevention of unexplained RSA.

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LZ and XL: Conceptualization; Methodology; Funding acquisition; Investigation; Writing—original draft; LG: Project administration; Validation;Resources; CR: Data curation: Supervision; HZ: Formal analysis: Software; LZ, XL, CR, HZ and LG Writing—review & editing; Investigation All authors read and approved the final manuscript.

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Correspondence to Li Gao.

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All of the subjects had agreed with the informed consents and the procedures in this study were supervised by Liaocheng Dongchangfu District Maternal and Child Health Hospital’ ethics committee. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Written informed consent was obtained from the parents.

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Zhao, L., Liu, X., Ren, C. et al. Silencing of LncRNA SNHG6 protects trophoblast cells through regulating miR-101-3p/OTUD3 axis in unexplained recurrent spontaneous abortion. J Mol Histol 53, 871–882 (2022). https://doi.org/10.1007/s10735-022-10102-9

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  • DOI: https://doi.org/10.1007/s10735-022-10102-9

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