Circular RNA hsa_circ_0081343 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-210-5p/DLX3 axis

Reproductive Biology and Endocrinology

Jing Li¹  Hui Wang²  Jiansheng Xie²  Caiqun Luo²  Xiaoxia Wu²  Jianming Zhang³  Zhiyong Xu⁴  Bohong Li⁴  Yang Liu⁴ 

[1] Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University;Department of Obstetrics and Gynecology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University;Institute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University;Medical genetic center, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University;

关键词: Circular RNA;    hsa_circ_0081343;    Fetal growth restriction;    HTR-8;    Competing endogenous RNA;    miR-210-5p;   

DOI  :  10.1186/s12958-021-00795-0

来源: DOAJ

【 摘 要 】

Abstract Background Various circular RNAs (circRNAs) are dysregulated in the placenta of fetal growth restriction (FGR) fetuses, but their roles and regulatory mechanisms have not been fully elucidated. Herein, we aimed to elucidate the role of hsa_circ_0081343 in regulating the migration, invasion, and apoptosis of human extravillous trophoblast HTR-8 cells. Methods CircRNA and miRNA levels were examined by quantitative reverse transcription PCR (qRT-PCR). Overexpression plasmid constructs and siRNAs were used to overexpress and knockdown hsa_circ_0081343, respectively. Transwell assays and flow cytometry analyses were performed to evaluate the effects of hsa_circ_0081343 or miR-210-5p on migration, invasion, and apoptosis. Protein levels were analyzed by western blotting. Dual luciferase activity and anti-AGO2 RNA immunoprecipitation (RIP) assays were performed to identify the relationship between miR-210-5p and hsa_circ_0081343. Results Hsa_circ_0081343 expression was significantly downregulated in 37 FGR placental tissues compared to healthy placental control tissues. Hsa_circ_0081343 overexpression may inhibit apoptosis by downregulating the expression of cleaved caspase 3 and caspase 9 and alleviating the migration and invasion of HTR-8 cells by inducing the expression of MMP2 and MMP9. The dual luciferase activity and anti-AGO2 RIP assay results showed that hsa_circ_0081343 binds to miR-210-5p. miR-210-5p overexpression eliminated the effect of hsa_circ_0081343 overexpression in HTR-8 cells. Finally, DLX3 was identified as a direct target of miR-210-5p. Conclusions hsa_circ_0081343 expression levels are significantly downregulated in FGR placental tissues. Hsa_circ_0081343 regulates the migration, invasion, and apoptosis of HTR-8 cells via the hsa-miR-210-5p/DLX3 axis.

【 授权许可】

Unknown