Key Lab of Etiology and Epidemiology, National Health Commission & Education Bureau of Heilongjiang Province (23618504), Key Laboratory of Trace Elements and Human Health, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China.
Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Endocrinol (Lausanne). 2024 Oct 31;15:1407859. doi: 10.3389/fendo.2024.1407859. eCollection 2024.
Goiter related to excessive iodine nutrition remains a significant public health issue in some countries. There has been no reported study on long noncoding RNAs (lncRNAs) related to goiters. In this study, goiter was induced by drinking water with excess iodine for 10 or 20 weeks in Kunming mice. Whole transcriptome sequencing results showed that LNC89 expression increased in mice goiter tissues compared to normal thyroid tissues and higher in 20 weeks goiter tissues than in 10 weeks goiter tissues, which were identified by qRT-PCR. Cooperate with human-mouse homologous gene conversion, a new LNC89/LNC60-Col11a2 axis was predicted by LncTar and expression correlation analysis based on whole transcriptome sequencing results. Increased Col11a2 expression was also identified by qRT-PCR and Western blot in the mice goiter tissues. In the human normal thyroid cell line Nthy-ori-3 treated with KI0, LNC60 and Col11a2 expression increased with promoted cell viability, which were reversed by siLNC60 treatment. Furthermore, LNC60 and Col11a2 mRNA levels were found increased in peripheral blood of nodular goiter patients from high water iodine areas of China and have high diagnostic values for nodular goiter while AUC of LNC60 and Col11a2 are 89.97% and 84.85%, respectively. In conclusion, the novel LNC89/LNC60-Col11a2 axis may be involved in the progression of goiter related to iodine excess, providing potential biomarkers and therapeutic targets in the future.
碘营养过剩导致的甲状腺肿仍然是一些国家的重大公共卫生问题。目前尚未有关于与甲状腺肿相关的长链非编码 RNA(lncRNA)的报道研究。在这项研究中,昆明小鼠通过饮用过量碘水 10 或 20 周来诱导甲状腺肿。全转录组测序结果显示,与正常甲状腺组织相比,lncRNA89(LNC89)在甲状腺肿组织中的表达增加,并且 20 周甲状腺肿组织中的表达高于 10 周甲状腺肿组织,这一点通过 qRT-PCR 得到了验证。通过 LncTar 和全转录组测序结果的表达相关性分析,结合人与鼠同源基因转换,预测了一个新的 LNC89/LNC60-Col11a2 轴。qRT-PCR 和 Western blot 结果也显示,在碘过量诱导的小鼠甲状腺肿组织中 Col11a2 的表达增加。在 KI0 处理的人正常甲状腺细胞系 Nthy-ori-3 中,LNC60 和 Col11a2 的表达增加,细胞活力增强,而 siLNC60 处理则逆转了这一结果。此外,在中国高水碘地区结节性甲状腺肿患者的外周血中发现 LNC60 和 Col11a2 的 mRNA 水平升高,对结节性甲状腺肿具有较高的诊断价值,而 LNC60 和 Col11a2 的 AUC 分别为 89.97%和 84.85%。综上所述,新型 LNC89/LNC60-Col11a2 轴可能参与了碘过量相关甲状腺肿的发生发展,为未来提供了潜在的生物标志物和治疗靶点。