{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:40:06Z","timestamp":1790278806628,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T00:00:00Z","timestamp":1497830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["816708028"],"award-info":[{"award-number":["816708028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370967\/H0724"],"award-info":[{"award-number":["81370967\/H0724"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2016ZX310182"],"award-info":[{"award-number":["2016ZX310182"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Folic acid deficiency during pregnancy is believed to be a high\u2010risk factor for neural tube defects (<jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s). Disturbed epigenetic modifications, including mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> regulation, have been linked to the pathogenesis of <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s in those with folate deficiency. However, the mechanism by which folic acid\u2010regulated mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> influences this pathogenesis remains unclear. It is believed that <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation is associated with dysregulated mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression. To clarify this issue, here we measured the methylation changes of 22 mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s in 57 human <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> cases to explore whether such changes are involved in mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> regulation in <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> cases through folate metabolism. In total, eight of the 22 mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s tested reduced their methylation modifications in <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> cases, which provide direct evidence of the roles of interactions between <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation and mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> level in these defects. Among the findings, there was a significant association between folic acid concentration and hsa\u2010let\u20107 g methylation level in <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> cases. Hypomethylation of hsa\u2010let\u20107 g increased its own expression level in both <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content> cases and cell models, which indicated that hsa\u2010let\u20107 g methylation directly regulates its own expression. Overexpression of hsa\u2010let\u20107 g, along with its target genes, disturbed the migration and proliferation of <jats:styled-content style=\"fixed-case\">SK<\/jats:styled-content>\u2010N\u2010<jats:styled-content style=\"fixed-case\">SH<\/jats:styled-content> cells, implying that hsa\u2010let\u20107 g plays important roles in the prevention of <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s by folic acid. In summary, our data suggest a relationship between aberrant methylation of hsa\u2010let\u20107 g and disturbed folate metabolism in <jats:styled-content style=\"fixed-case\">NTD<\/jats:styled-content>s, implying that improvements in nutrition during early pregnancy may prevent such defects, possibly <jats:italic>via<\/jats:italic> the donation of methyl groups for mi<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s.<\/jats:p>","DOI":"10.1111\/jcmm.13228","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T01:53:16Z","timestamp":1497923596000},"page":"3244-3253","source":"Crossref","is-referenced-by-count":23,"title":["Folate deficiency disturbs hsa\u2010let\u20107 g level through methylation regulation in neural tube defects"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1918-0040","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaofang","family":"Shangguan","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xin","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyan","family":"Chang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Lu","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Niu","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Municipal Key Laboratory of Child Development and Nutriomics Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1181"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/132.8.2457S"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-006-6095-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01436"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.16.4454"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.4.1618"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00212-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1999.9227"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01122"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-2-10"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.989402"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20623"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a137250"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1988.03410210053035"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199212243272602"},{"issue":"8","key":"e_1_2_8_17_1","first-page":"1","article-title":"Sonic Hedgehog Signaling Affected by Promoter Hypermethylation Induces Aberrant Gli2 Expression in Spina Bifida","volume":"53","author":"Lu XL","year":"2015","journal-title":"Mol Neurobiol"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.11.023"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.01.014"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2540"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.08.002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507425103"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.354"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.36"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molonc.2012.07.007"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-6-6"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.783108"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.6.8.4486"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0441"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-9-r68"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl476"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.8.8.971"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.036"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph10094352"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.2009.28858"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08089.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-09-0163"},{"key":"e_1_2_8_38_1","first-page":"151","article-title":"miRNAs as modulators of angiogenesis","volume":"3","author":"Landskronereiger S","year":"2013","journal-title":"Cold Spring Harb Perspect Med"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33680"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.012237"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.000745"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-012369"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42980"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-276428"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.13228","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T15:33:58Z","timestamp":1696174438000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.13228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,19]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1111\/jcmm.13228"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.13228","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,19]]}}}