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Characterization of CircRNA-Associated CeRNA Networks in Folate Deficiency-Induced Neural Tube Defects

生物医学与环境科学:英文版 2023年第9期36卷 837-849页

作者： WANG Shan ZENG Yu Bing PEI Pei HE Xue Jia LIU Fan WANG Yi ZHANG Ting Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of PediatricsBeijing 100020China Capital Institute of Pediatrics-Peking University Teaching Hospital Beijing 100020China Children's Hospital Capital Institute of Pediatrics Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100020China

Objective Circular RNAs(circRNAs)participate in several important pathological processes and have been used in the diagnosis and treatment of various diseases.This study aimed to investigate the role of circRNAs in neural tube defects(NTDs).Method We characterized circRNA-associated competitive endogenous RNA(ceRNA)networks in brain tissue of low folate-induced NTDs mouse at embryonic day 13.5 by high-throughput sequencing.The expression levels of circzfp644,miR-20-5p and Gas7 were detected by RT-PCR.Gas7 and circzfp644functions were determined by miRNA-mimics and inhibitors in mouse teratocarcinoma cells(F9 cells),and luciferase gene reporter assay was assessed in the F9 cells.In addition,the expression levels of circzfp644,miR-20-5p and Gas7 were determined by Nanostring in human NTDs tissues.Results We detected 57 circRNA transcripts,16 miRNAs,and 148 mRNAs that were significantly dysregulated in NTDs brain tissues compared with their expression levels in control(normal)tissues.circzfp644 shared miRNA response elements with the growth arrest specific 7(Gas7)gene and competitively bound with miR-20-5p to increase the expression of Gas7.Downregulation of circzfp644and Gas7 and upregulation of miR-20-5p were found in human NTD tissue.Conclusion This study provides new perspectives on the role of circRNAs in nervous system development and the pathogenesis of NTDs.

关键词： circzfp644 Gas7 miR-20-5p Folate deficiency NTDs

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