RSK4基因甲基化与甲状腺乳头状癌的关系

Q4 Medicine

中华内分泌代谢杂志 Pub Date : 2019-12-25 DOI:10.3760/CMA.J.ISSN.1000-6699.2019.12.007

Yanan Yin, Jia-rui Yu, J. Chi, K. Che, Zhou Huai, Yangang Wang, F. Wang, Shi-hua Zhao

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引用次数: 0

摘要

目的检测甲状腺乳头状癌（PTC）中核糖体S6激酶4（RSK4）的甲基化状态，并探讨其与mRNA表达及临床特征的相关性。方法收集134例PTC组织及相应的癌旁甲状腺组织。通过甲基化特异性PCR和亚硫酸氢盐基因组测序分析PTC组织和相应癌旁组织中RSK4基因的DNA甲基化状态，并通过实时定量PCR检测mRNA表达。分析DNA甲基化状态与mRNA表达和临床特征的关系。结果经甲基化特异性PCR和亚硫酸氢盐基因组测序，PTC组织中RSK4的甲基化率显著高于癌旁组织（P＜0.05），甲基化组RSK4mRNA表达低于非甲基化组（P<0.01），甲基化PTC中RSK4mRNA水平低于甲基化癌旁组织（P<0.01）；未甲基化PTC中RSK4 mRNA水平也低于未甲基化的癌旁组织（P<0.01），结论RSK4启动子CpG岛的高甲基化可能是PTC中RSK4低表达的机制之一，可作为早期诊断和治疗的分子靶点。关键词：甲状腺乳头状癌；核糖体S6激酶4；甲基化

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Relationship between methylation of RSK4 gene and papillary thyroid carcinoma

Objective To detect the methylation status of ribosomal S6 kinase 4 (RSK4)in papillary thyroid carcinoma (PTC)and to study its correlation with mRNA expression and clinical features. Methods 134 cases PTC tissues and corresponding paracancerous thyroid tissues were collected. DNA methylation status of RSK4 gene in PTC tissues and corresponding paracancerous tissues were analyzed by methylation specific PCR and bisulfite genomic sequencing, and mRNA expression was detected by quantitative realtime PCR. The relationship of DNA methylation status with mRNA expression and clinical features was analyzed. Results The methylation rate of RSK4 in PTC tissues was significantly higher than that in paracancerous tissues by methylation specific PCR (P<0.05)and bisulfite genomic sequencing (P<0.01). The RSK4 mRNA level in PTC tissues was significantly lower than that in paracancerous tissues (P<0.01). In PTC tissues, RSK4 mRNA expression in methylation group was lower than that in unmethylation group (P<0.01). The RSK4 mRNA level in PTC of methylation was lower than that in paracancerous tissues of methylation (P<0.01); the RSK4 mRNA level in PTC of unmethylation was also lower than that in paracancerous tissues of unmethylated ones (P<0.01). There was relationship of RSK4 hypermethylation with lymphatic metastasis and TNM grade (P<0.05). Serum concentrations of thyroid stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody in methylation group were higher than those in unmethylation group (P<0.05). Conclusion The hypermethylation of RSK4 promoter′s CpG islands might be one of the mechanisms for poor expression of RSK4 in PTC, which may serve as a molecular target of early diagnosis and treatment. Key words: Papillary thyroid carcinoma; Ribosomal S6 kinase 4; Methylation

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来源期刊

中华内分泌代谢杂志 Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

0.60

自引率

0.00%

发文量

7243

期刊介绍： The Chinese Journal of Endocrinology and Metabolism was founded in July 1985. It is a senior academic journal in the field of endocrinology and metabolism sponsored by the Chinese Medical Association. The journal aims to be the "Chinese broadcaster of new knowledge on endocrinology and metabolism worldwide". It reports leading scientific research results and clinical diagnosis and treatment experience in endocrinology and metabolism and related fields, as well as basic theoretical research that has a guiding role in endocrinology and metabolism clinics and is closely integrated with clinics. The journal is a core journal of Chinese science and technology (a statistical source journal of Chinese science and technology papers), and is included in Chinese and foreign statistical source journal databases such as the Chinese Science and Technology Papers and Citation Database, Chemical Abstracts, and Scopus.