MiR-150-5p contributes to unexplained recurrent spontaneous abortion by targeting VEGFA and downregulating the PI3K/AKT/mTOR signaling pathway

• Published in: Journal of assisted reproduction and genetics Vol. 41; no. 1; pp. 63 - 77
• Main Authors: Liao, Wenyan, Deng, Xin, Chen, Guodong, Yang, Juanli, Li, Yi, Li, Li, Zhong, Lili, Tao, Guangwei, Hou, Jiafeng, Li, Mujun, Ding, Chengming
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2024; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; Abortion, Spontaneous; AKT protein; Animals; Cell migration; Cell Proliferation; Endometrium; Female; Fetal resorption; Fibroblast growth factor 2; Gene expression; Gynecology; Hospitals; Human Genetics; Humans; Medicine; Medicine & Public Health; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Miscarriage; Obstetrics; Pathogenesis; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Physiology; Pregnancy; Proto-Oncogene Proteins c-akt - genetics; Reproductive Medicine; Reproductive Physiology and Disease; Signal transduction; Signal Transduction - genetics; TOR protein; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Uterus; Vascular Endothelial Growth Factor A - genetics; Womens health; Unexplained recurrent spontaneous abortions (URSA); PI3K/AKT/mTOR signaling pathway; miR-150-5p; VEGFA
• ISSN: 1058-0468; 1573-7330
• DOI: 10.1007/s10815-023-02959-w

Purpose The purpose of this study is to investigate the function of miR-150-5p in URSA. Method Twenty-six chorionic villous tissues were collected to examine the expression of miR-150-5p and VEGFA by using quantitative polymerase chain reaction (qPCR) and western blot assay, respectively. Transwell assay was conducted to assess the migration and invasion ability of trophoblast cells. The dual-luciferase reporter assay was applied to determine the relationship between miR-150-5p and VEGFA in vitro. Relevant signaling pathway protein expression level was measured via western blot assay. Signaling transduction inhibitor LY294002 was used to block PI3K/AKT/mTOR signaling pathway. Finally, in vivo the effect of miR-150-5p on embryonic absorption rate was evaluated in mice. Results Clinical samples revealed that miR-150-5p expression was significantly elevated in the villous tissues and serum of URSA patients. Moreover, the overexpressing of miR-150-5p could inhibit both HTR-8/SVneo cell and JAR cell migration, invasion, and restrained PI3K/AKT/mTOR signaling pathway by targeting VEGFA in vitro. This inhibitory effect of miR-150-5p could be reversed by overexpressing the gene of vascular epithelial growth factor A ( VEGFA ). In contrary, inhibition of miR-150-5p significantly enhanced migration, invasion ability of both HTR-8/SVneo and JAR cells, and also could stimulate PI3K/AKT/mTOR signaling pathway. This promoting effect of miR-150-5p could be ameliorated by LY294002 (PI3K inhibitor). Finally, after miR-150-5p overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. Conclusions Overall, these findings imply that miR-150-5p is among the key factors that regulate the pathogenesis of URSA.