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甲状旁腺肿瘤中微小RNA失调提示胚胎特征。

MicroRNA deregulation in parathyroid tumours suggests an embryonic signature.

作者信息

Verdelli C, Forno I, Vaira V, Corbetta S

机构信息

Laboratory of Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy.

Division of Pathology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

J Endocrinol Invest. 2015 Apr;38(4):383-8. doi: 10.1007/s40618-014-0234-y. Epub 2015 Jan 11.

DOI:10.1007/s40618-014-0234-y
PMID:25577262
Abstract

Primary hyperparathyroidism is a common endocrine disorder caused by abnormal tumour parathyroid cell proliferation. Parathyroid tumours show a great variability both in clinical features, such as the severity of PTH secretion, the rate and the pattern of cell proliferation, and genetic background. Studies aiming to develop new diagnostic markers and therapeutic approaches need a deeper definition of this variability. Dysregulation of microRNAs (miRNAs) has been shown to play an essential role in the development and progression of cancer. MiRNAs are small noncoding RNAs that inhibit the translation and stability of messenger RNAs (mRNAs). Here, data about the miRNA expression pattern in parathyroid normal and tumour glands were reviewed. Though available data in parathyroid tumours are very limited, the expression pattern of a subset of specific miRNAs clearly discriminated parathyroid carcinomas from normal parathyroid glands and, more clinically relevant, from parathyroid adenomas. Investigation showed that parathyroid tumours were characterized by an embryonic expression pattern of miRNAs such as miR-296, or the miRNA clusters C19MC and miR-371-3, typically in stem cells committed to differentiation or during human embryonic development, respectively. Further, miRNA profiles were correlated with tumour aggressive behaviour. Moreover, the interaction with the oncosuppressor menin suggests that miRNAs might modulate the function of the known oncosuppressors or oncogenes involved in parathyroid tumourigenesis and thus overseeing the tumour phenotype. In conclusion, miRNAs might provide new diagnostic markers and new therapeutic approaches by developing molecular miRNA-targeted therapies for the cure of parathyroid tumours, whose unique option is surgery.

摘要

原发性甲状旁腺功能亢进是一种常见的内分泌疾病,由甲状旁腺肿瘤细胞异常增殖引起。甲状旁腺肿瘤在临床特征(如甲状旁腺激素分泌的严重程度、细胞增殖速率和模式)以及遗传背景方面存在很大差异。旨在开发新诊断标志物和治疗方法的研究需要对这种差异有更深入的定义。微小RNA(miRNA)失调已被证明在癌症的发生和发展中起重要作用。miRNA是小的非编码RNA,可抑制信使RNA(mRNA)的翻译和稳定性。在此,我们综述了甲状旁腺正常组织和肿瘤组织中miRNA表达模式的数据。尽管甲状旁腺肿瘤的现有数据非常有限,但特定miRNA子集的表达模式能明显区分甲状旁腺癌与正常甲状旁腺组织,更具临床相关性的是,还能区分甲状旁腺癌与甲状旁腺腺瘤。研究表明,甲状旁腺肿瘤的特征是miRNA的胚胎表达模式,如miR-296,或miRNA簇C19MC和miR-371-3,它们分别典型地出现在致力于分化的干细胞中或人类胚胎发育期间。此外,miRNA谱与肿瘤侵袭性行为相关。而且,与抑癌蛋白menin的相互作用表明,miRNA可能调节参与甲状旁腺肿瘤发生的已知抑癌基因或癌基因的功能,从而控制肿瘤表型。总之,miRNA可能通过开发针对miRNA的分子疗法为甲状旁腺肿瘤的治疗提供新的诊断标志物和新的治疗方法,而甲状旁腺肿瘤目前唯一的治疗选择是手术。

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