{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:36Z","timestamp":1787008896503,"version":"build-2736575974"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["119\u20133120624549"],"award-info":[{"award-number":["119\u20133120624549"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Makorin RING finger protein 3 (MKRN3) is a key inhibitor of the hypothalamic\u2013pituitary-gonadal (HPG) axis. The association between MKRN3 gene variants and central precocious puberty (CPP) has been repeatedly examined. In a recent study, MKRN3 has been assigned a role of tumor suppressor in lung carcinogenesis. Therefore, it is hypothesized that MKRN3 may be the link between CPP and lung cancer (LC), and certain MKRN3 gene variants may affect individuals' susceptibility to CPP and LC. The rs12441287, rs6576457 and rs2239669 in the MKRN3 gene were selected as the target variants. Sanger sequencing was applied to genotype them in two sets of case\u2013control cohorts, namely 384 CPP girls and 422 healthy girls, 550 LC patients and 800 healthy controls. The results showed that rs6576457 but not rs12441287 or rs2239669 was significantly associated with the risk of CPP and LC. Their association with CPP risk was further confirmed in the following meta-analysis. Subsequent functional assays revealed that the rs6576457 genotypes were correlated with differentially expressed MKRN3, and the rs6576457 alleles affected the transcription repressor Oct-1 binding affinity to the MKRN3 promoter. Collectively, the MKRN3 gene rs6576457 may participate in the CPP pathology and LC tumorigenesis in the Hubei Chinese population. However, the present findings should be validated in additional investigations with larger samples from different ethnic populations.<\/jats:p>","DOI":"10.1093\/hmg\/ddae131","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T18:40:49Z","timestamp":1724956849000},"page":"1930-1938","source":"Crossref","is-referenced-by-count":3,"title":["The rs6576457 G\u2009&amp;gt;\u2009A variant in the\n                    <i>MKRN3<\/i>\n                    gene promoter significantly increases the risk of central precocious puberty and lung cancer in Hubei Chinese population"],"prefix":"10.1093","volume":"33","author":[{"given":"Feng","family":"Wu","sequence":"first","affiliation":[{"name":"Wuhan University of Technology Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]},{"name":"Wuhan University of Technology Institute of WUT-AMU, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengchu","family":"Yue","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Institute of WUT-AMU, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyuan","family":"Deng","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Institute of WUT-AMU, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqiang","family":"Kang","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Institute of WUT-AMU, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyan","family":"Yu","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Institute of WUT-AMU, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Institute of WUT-AMU, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bixin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhong","family":"Feng","sequence":"additional","affiliation":[{"name":"Wuhan Xinzhou District People's Hospital Department of Clinical Laboratory, , 61 Xinzhou Road, Xinzhou District, Wuhan, Hubei 431400,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiantao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Maternal and Child Health Hospital of Hubei Province Department of Laboratory, , 745 Wuluo Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5482-1910","authenticated-orcid":false,"given":"Bifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Wuhan University of Technology Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]},{"name":"Wuhan University of Technology Institute of WUT-AMU, , 122 Luoshi Road, Hongshan District, Wuhan, Hubei 430070,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"2024111214310726700_ref1","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1056\/NEJMoa1302160","article-title":"Central precocious puberty caused by mutations in the imprinted gene MKRN3","volume":"368","author":"Abreu","year":"2013","journal-title":"N Engl J Med"},{"key":"2024111214310726700_ref2","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1186\/1471-2164-11-721","article-title":"The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene","volume":"11","author":"B\u00f6hne","year":"2010","journal-title":"BMC Genomics"},{"key":"2024111214310726700_ref3","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/hmg\/8.5.795","article-title":"Imprinting of a RING zinc-finger encoding gene in the mouse chromosome region homologous to the Prader-Willi syndrome genetic region","volume":"8","author":"Jong","year":"1999","journal-title":"Hum Mol Genet"},{"key":"2024111214310726700_ref4","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/nsr\/nwaa023","article-title":"MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3","volume":"7","author":"Li","year":"2020","journal-title":"Natl Sci Rev"},{"key":"2024111214310726700_ref5","doi-asserted-by":"crossref","first-page":"3796","DOI":"10.1093\/nar\/gkab155","article-title":"MKRN3-mediated ubiquitination of poly(A)-binding proteins modulates the stability and 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