A novel role of FoxO3a in the migration and invasion of trophoblast cells: from metabolic remodeling to transcriptional reprogramming

作者全名："Chen, Hao; Wang, Shi-Han; Chen, Chang; Yu, Xin-Yang; Zhu, Jia-Nan; Mansell, Toby; Novakovic, Boris; Saffery, Richard; Baker, Philip N.; Han, Ting-Li; Zhang, Hua"

作者地址："[Chen, Hao; Wang, Shi-Han; Chen, Chang; Yu, Xin-Yang; Zhu, Jia-Nan; Zhang, Hua] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China; [Chen, Hao; Wang, Shi-Han; Chen, Chang; Yu, Xin-Yang; Zhu, Jia-Nan; Baker, Philip N.; Zhang, Hua] Chongqing Med Univ, Canada China New Zealand Joint Lab Maternal & Fet, Chongqing, Peoples R China; [Chen, Hao; Wang, Shi-Han; Zhu, Jia-Nan] Chongqing Key Lab OfTranslat Med Major Metab Dis, Chongqing, Peoples R China; [Chen, Chang] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China; [Han, Ting-Li] Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400010, Peoples R China; [Mansell, Toby; Novakovic, Boris; Saffery, Richard] Univ Melbourne, Mol Immun, Murdoch Childrens Res Inst, Melbourne, Vic, Australia; [Mansell, Toby; Novakovic, Boris; Saffery, Richard] Univ Melbourne, Dept Paediatr, Melbourne, Vic, Australia; [Baker, Philip N.] Univ Leicester, Coll Med Biol Sci & Psychol, Leicester, Leics, England"

通信作者："Zhang, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet & Gynecol, Chongqing 400016, Peoples R China.; Han, TL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400010, Peoples R China."

来源：MOLECULAR MEDICINE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000837689800002

JCR分区：Q1

影响因子：5.7

年份：2022

卷号：28

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Preeclampsia; Forkhead box O3a protein; Aromatic amino acid; Long-chain unsaturated fatty acid; Migration

摘要："Background The forkhead box O3a protein (FoxO3a) has been reported to be involved in the migration and invasion of trophoblast, but its underlying mechanisms unknown. In this study, we aim to explore the transcriptional and metabolic regulations of FoxO3a on the migration and invasion of early placental development. Methods Lentiviral vectors were used to knock down the expression of FoxO3a of the HTR8/SVneo cells. Western blot, matrigel invasion assay, wound healing assay, seahorse, gas-chromatography-mass spectrometry (GC-MS) based metabolomics, fluxomics, and RNA-seq transcriptomics were performed. Results We found that FoxO3a depletion restrained the migration and invasion of HTR8/SVneo cells. Metabolomics, fluxomics, and seahorse demonstrated that FoxO3a knockdown resulted in a switch from aerobic to anaerobic respiration and increased utilization of aromatic amino acids and long-chain fatty acids from extracellular nutrients. Furthermore, our RNA-seq also demonstrated that the expression of COX-2 and MMP9 decreased after FoxO3a knockdown, and these two genes were closely associated with the migration/invasion progress of trophoblast cells. Conclusions Our results suggested novel biological roles of FoxO3a in early placental development. FoxO3a exerts an essential effect on trophoblast migration and invasion owing to the regulations of COX2, MMP9, aromatic amino acids, energy metabolism, and oxidative stress."

基金机构："National Natural Science Foundation of China [81971406, 8177 1607, 81871185, 81901507, 81961128004]; 111 Project [(2016)32]; Chongqing Health Commission [2018ZDXM024]; Chongqing Health Commission and Chongqing Science & Technology Commission [2021MSXM121, 2020MSXM101, KJZD-K202100407]"

基金资助正文："The National Natural Science Foundation of China (No. 81971406, 8177 1607, 81871185, 81901507, 81961128004), The 111 Project (Yuwaizh uan (2016)32), Chongqing Health Commission (2018ZDXM024), Chongqing Health Commission and Chongqing Science & Technology Commission (2021MSXM121, 2020MSXM101, KJZD-K202100407)."