Effects of hsa_circ_0019217 on the biological functions of human trophoblast cells and its mechanism in pre-eclampsia
10.3760/cma.j.cn112141-20250525-00232
- VernacularTitle:hsa_circ_0019217对人绒毛外滋养细胞生物学功能的影响及其在子痫前期发生中的机制研究
- Author:
Ruting SHI
1
;
Yanqi CHEN
1
;
Huina LIU
1
;
Mengwei LI
1
;
Yiming WANG
1
Author Information
1. 郑州大学第一附属医院妇产科，郑州 450052
- Publication Type:Journal Article
- Keywords:
RNA, circular;
MicroRNAs;
Trophoblasts;
Cell proliferation;
Cell movement;
Pre-eclampsia
- From:
Chinese Journal of Obstetrics and Gynecology
2025;60(11):876-889
- CountryChina
- Language:Chinese
-
Abstract:
Objectives:To investigate the effect of circular RNA (circRNA) hsa_circ_0019217 on the biological function of chorionic trophoblast cell line (HTR8/SVneo) and its mechanism in the occurrence of pre-eclampsia (PE).Methods:The circRNA expression database was used to analyze the differentially expressed circRNA in placental tissues of PE women. The expression levels of hsa_circ_0019217 and miR-526b-5p were detected by reverse transcription real-time fluorescent quantitative PCR (RT-qPCR), and the subcellular localization of hsa_circ_0019217 was detected by fluorescence in situ hybridization. The proliferation, migration and invasion of trophoblast cells were detected by cell counting kit-8 (CCK-8) assay and transwell assay. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to verify the effects of hsa_circ_0019217, miR-526b-5p and decorin (DCN) on matrix metalloproteinase 2 (MMP2), tissue inhibitor of metalloproteinase 2 (TIMP2), placental growth factor (PlGF) and human chorionic gonadotropin (hCG) protein expression levels. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used to verify the interaction between hsa_circ_0019217, miR-526-5p and DCN.Results:(1) The analysis of circRNA expression database showed that the expression level of hsa_circ_0019217 was significantly increased in the placental tissues of PE women (fold change=67, P<0.05), and it was mainly located in the cytoplasm. (2) Knockdown of hsa_circ_0019217 promoted the proliferation, migration and invasion of HTR8/SVneo cells, increased the expression levels of MMP2 and PlGF, and decreased the expression levels of TIMP2 and hCG in HTR8/SVneo cells. (3) Hsa_circ_0019217 targeted adsorption of miR-526b-5p, and inhibition of miR-526b-5p reduced the proliferation, migration and invasion of HTR8/SVneo cells. The expression levels of MMP2 and PlGF in HTR8/SVneo cells were increased, and the expression levels of TIMP2 and hCG were decreased. Hsa_circ_0019217 knockdown and inhibiting miR-526b-5p could reverse the effect of hsa_circ_0019217 knockdown on promoting the proliferation, migration and invasion of HTR8/SVneo cells, and reversed the effect of hsa_circ_0019217 knockdown on the protein expression levels of MMP2, PlGF, TIMP2 and hCG. (4) miR-526b-5p targeted DCN in HTR8/SVneo cells, hsa_circ_0019217 knockdown reduced the expression level of DCN, and inhibiting miR-526b-5p increased the expression level of DCN. When hsa_circ_0019217 and miR-526b-5p were inhibited simultaneously, there was no significant change in the protein expression level of DCN. (5) Overexpression of miR-526b-5p promoted the proliferation, migration and invasion of HTR8/SVneo cells, while overexpression of DCN inhibited the proliferation, migration and invasion of HTR8/SVneo cells. Simultaneous overexpression of miR-526b-5p and DCN reversed the effects of miR-526b-5p overexpression on cell proliferation, migration and invasion. Overexpression of miR-526b-5p increased the expression levels of MMP2 and PlGF and decreased the expression levels of TIMP2 and hCG in HTR8/SVneo cells. Overexpression of DCN reduced the expression levels of MMP2 and PlGF and increased the expression levels of TIMP2 and hCG. Overexpression of miR-526b-5p and DCN reversed the effects of miR-526b-5p on the expression of these proteins. Conclusion:Hsa_circ_0019217 regulates the expression of DCN by adsorption of miR-526b-5p, thereby affecting the proliferation, migration and invasion of trophoblast cells and regulating the protein expression levels of MMP2, TIMP2, PlGF and hCG, which might be used as a target for early prevention of PE.
