Role and molecular mechanism of insulin-like growth factor 2 mRNA-binding protein 3 in pathogenesis of preeclampsia
- VernacularTitle:胰岛素样生长因子2-mRNA结合蛋白3在子痫前期发病中的作用及其分子机制
- Author:
Ling ZHAO
1
;
Shasha LIN
;
Xiaowei ZHANG
;
Wenbai ZHOU
Author Information
- Keywords: insulin-like growth factor 2 mRNA-binding protein 3; N6-adenosine methyla-tion; placenta; preeclampsia; trophocyte; cell proliferation; cell cycle; transcriptome
- From: Journal of Clinical Medicine in Practice 2025;29(15):92-100
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the role and potential molecular mechanisms of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3)in preeclampsia(PE).Methods The expres-sion of IGF2BP3 in placental tissues from patients with PE was detected using quantitative reverse transcription polymerase chain reaction.IGF2BP3 was knocked down via RNA interference technology to evaluate its effects on the proliferation,invasion,apoptosis and cell cycle of HTR-8/SVneo and JEG-3 trophoblast cell lines.Transcriptome sequencing was employed to analyze changes in cellular biological functions and the stability of the potential downstream molecule circPAPPA following IGF2BP3 interference.RNA binding protein immunoprecipitation(RIP)and fluorescence in situ hy-bridization(FISH)were utilized to validate the direct targeting relationship between IGF2BP3 and circPAPPA.Results IGF2BP3 was significantly downregulated in PE placentas.Knockdown of IGF2BP3 inhibited trophoblast cell proliferation and invasion,promoted cell apoptosis and cellcycle arrest.Functional enrichment analysis revealed that IGF2BP3 was involved in invasion and hypoxia response,regulating signaling pathways such as phosphatidylinositol-3-kinase(PI3K),mitogen-activated protein kinase(MAPK)and hypoxia-inducible factor-1(HIF-1).Knockdown of IGF2BP3 led to a reduction in circPAPPA stability,and RIP and FISH experiments confirmed the direct targeting rela-tionship between IGF2BP3 and circPAPPA.Conclusion IGF2BP3 is downregulated in PE and reg-ulates the stability of circPAPPA in an N6-adenosine methylation(m6A)-dependent manner,there-by affecting trophoblast cell function.
