Tong Yang, Jianguo Hu, Lei Zhang, Li Liu, Xin Pan, Yanqiu Zhou, Yi Wu, Xian Shi, Chidera N. Obiegbusi, Xiaojing Dong
{"title":"在胎儿生长受限过程中,CircCUL1通过ANXA1/PI3K/AKT轴海绵化hsa-miR-30e-3p,抑制滋养层细胞的迁移和侵袭,并促进细胞自噬。","authors":"Tong Yang, Jianguo Hu, Lei Zhang, Li Liu, Xin Pan, Yanqiu Zhou, Yi Wu, Xian Shi, Chidera N. Obiegbusi, Xiaojing Dong","doi":"10.1002/jbt.23759","DOIUrl":null,"url":null,"abstract":"<p>Fetal growth restriction (FGR) severely affects the health outcome of newborns and represents a major cause of perinatal morbidity. The precise involvement of circCULT1 in the progression of FGR remains unclear. We performed next-generation sequencing and RT-qPCR to identify differentially expressed circRNAs in placental tissues affected by FGR by comparing them with unaffected counterparts. Edu, flow cytometry, and transwell assay were conducted to detect HTR8/SVneo cell's function in regard to cell proliferation, migration, and invasion. The interaction between circCUL1 and hsa-miR-30e-3p was assessed through dual-luciferase reporter assays, validation of the interaction between circCUL1 and ANXA1 was performed using RNA pulldown and immunoprecipitation assays. Western blot analysis was performed to evaluate protein levels of autophagy markers and components of the PI3K/AKT signaling pathway. A knockout (KO) mouse model was established for homologous mmu-circ-0001469 to assess fetal mouse growth and development indicators. Our findings revealed an upregulation of circCUL1 expression in placental tissues from patients with FGR. We found that suppression of circCUL1 increased the trophoblast cell proliferation, migration, and invasion, circCUL1 could interact with hsa-miR-30e-3p. Further, circCUL1 stimulated autophagy, modulating trophoblast cell autophagy via the ANXA1/PI3K/AKT pathway, and a notable disparity was observed, with KO mice displaying accelerated embryo development and exhibiting heavier placentas in comparison to wild-type C57BL/6 mice. By modulating the ANXA1/PI3K/AKT signaling pathway through the interaction with hsa-miR-30e-3p, circCUL1 promotes autophagy while concurrently suppressing trophoblast cell proliferation, migration, and invasion. These findings offer novel insights into potential diagnostic markers and therapeutic targets for FGR research.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CircCUL1 inhibits trophoblast cell migration and invasion and promotes cell autophagy by sponging hsa-miR-30e-3p in fetal growth restriction via the ANXA1/PI3K/AKT axis\",\"authors\":\"Tong Yang, Jianguo Hu, Lei Zhang, Li Liu, Xin Pan, Yanqiu Zhou, Yi Wu, Xian Shi, Chidera N. Obiegbusi, Xiaojing Dong\",\"doi\":\"10.1002/jbt.23759\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Fetal growth restriction (FGR) severely affects the health outcome of newborns and represents a major cause of perinatal morbidity. The precise involvement of circCULT1 in the progression of FGR remains unclear. We performed next-generation sequencing and RT-qPCR to identify differentially expressed circRNAs in placental tissues affected by FGR by comparing them with unaffected counterparts. Edu, flow cytometry, and transwell assay were conducted to detect HTR8/SVneo cell's function in regard to cell proliferation, migration, and invasion. The interaction between circCUL1 and hsa-miR-30e-3p was assessed through dual-luciferase reporter assays, validation of the interaction between circCUL1 and ANXA1 was performed using RNA pulldown and immunoprecipitation assays. Western blot analysis was performed to evaluate protein levels of autophagy markers and components of the PI3K/AKT signaling pathway. A knockout (KO) mouse model was established for homologous mmu-circ-0001469 to assess fetal mouse growth and development indicators. Our findings revealed an upregulation of circCUL1 expression in placental tissues from patients with FGR. We found that suppression of circCUL1 increased the trophoblast cell proliferation, migration, and invasion, circCUL1 could interact with hsa-miR-30e-3p. Further, circCUL1 stimulated autophagy, modulating trophoblast cell autophagy via the ANXA1/PI3K/AKT pathway, and a notable disparity was observed, with KO mice displaying accelerated embryo development and exhibiting heavier placentas in comparison to wild-type C57BL/6 mice. By modulating the ANXA1/PI3K/AKT signaling pathway through the interaction with hsa-miR-30e-3p, circCUL1 promotes autophagy while concurrently suppressing trophoblast cell proliferation, migration, and invasion. These findings offer novel insights into potential diagnostic markers and therapeutic targets for FGR research.</p>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.23759\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.23759","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
CircCUL1 inhibits trophoblast cell migration and invasion and promotes cell autophagy by sponging hsa-miR-30e-3p in fetal growth restriction via the ANXA1/PI3K/AKT axis
Fetal growth restriction (FGR) severely affects the health outcome of newborns and represents a major cause of perinatal morbidity. The precise involvement of circCULT1 in the progression of FGR remains unclear. We performed next-generation sequencing and RT-qPCR to identify differentially expressed circRNAs in placental tissues affected by FGR by comparing them with unaffected counterparts. Edu, flow cytometry, and transwell assay were conducted to detect HTR8/SVneo cell's function in regard to cell proliferation, migration, and invasion. The interaction between circCUL1 and hsa-miR-30e-3p was assessed through dual-luciferase reporter assays, validation of the interaction between circCUL1 and ANXA1 was performed using RNA pulldown and immunoprecipitation assays. Western blot analysis was performed to evaluate protein levels of autophagy markers and components of the PI3K/AKT signaling pathway. A knockout (KO) mouse model was established for homologous mmu-circ-0001469 to assess fetal mouse growth and development indicators. Our findings revealed an upregulation of circCUL1 expression in placental tissues from patients with FGR. We found that suppression of circCUL1 increased the trophoblast cell proliferation, migration, and invasion, circCUL1 could interact with hsa-miR-30e-3p. Further, circCUL1 stimulated autophagy, modulating trophoblast cell autophagy via the ANXA1/PI3K/AKT pathway, and a notable disparity was observed, with KO mice displaying accelerated embryo development and exhibiting heavier placentas in comparison to wild-type C57BL/6 mice. By modulating the ANXA1/PI3K/AKT signaling pathway through the interaction with hsa-miR-30e-3p, circCUL1 promotes autophagy while concurrently suppressing trophoblast cell proliferation, migration, and invasion. These findings offer novel insights into potential diagnostic markers and therapeutic targets for FGR research.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.