Makorin RING Finger 蛋白 3 (MKRN3) 是下丘脑-垂体-性腺 (HPG) 轴的关键抑制剂。 MKRN3 基因变异与中枢性性早熟 (CPP) 之间的关联已被反复研究。在最近的一项研究中，MKRN3 被认为在肺癌发生中发挥肿瘤抑制作用。因此，推测MKRN3可能是CPP和肺癌（LC）之间的联系，并且某些MKRN3基因变异可能影响个体对CPP和LC的易感性。选择MKRN3基因中的rs12441287、rs6576457和rs2239669作为目标变体。应用桑格测序对两组病例对照队列进行基因分型，即 384 名 CPP 女孩和 422 名健康女孩、550 名 LC 患者和 800 名健康对照。结果显示，rs6576457而非rs12441287或rs2239669与CPP和LC的风险显着相关。它们与 CPP 风险的关联在以下荟萃分析中得到进一步证实。随后的功能测定表明，rs6576457基因型与差异表达的MKRN3相关，并且rs6576457等位基因影响转录抑制子Oct-1与MKRN3启动子的结合亲和力。总的来说，MKRN3 基因 rs6576457 可能参与湖北人群的 CPP 病理和 LC 肿瘤发生。然而，目前的研究结果应该在来自不同种族人群的更大样本的额外调查中得到验证。© 作者 2024。由牛津大学出版社出版。版权所有。如需权限，请发送电子邮件至：journals.permissions@oup.com。

Makorin RING finger protein 3 (MKRN3) is a key inhibitor of the hypothalamic-pituitary-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-control 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.© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.