MicroRNAs in thyroid cancer - PubMed (original) (raw)

Review

. 2011 Nov;96(11):3326-36.

doi: 10.1210/jc.2011-1004. Epub 2011 Aug 24.

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Review

MicroRNAs in thyroid cancer

Albert de la Chapelle et al. J Clin Endocrinol Metab. 2011 Nov.

Abstract

Context: Traditionally, factors predisposing to diseases are either genetic ("nature") or environmental, also known as lifestyle-related ("nurture"). Papillary thyroid cancer is an example of a disease where the respective roles of these factors are surprisingly unclear.

Evidence acquisition: Original articles and reviews summarizing our current understanding of the role of microRNA in thyroid tumorigenesis are reviewed and evaluated.

Conclusion: The genetic predisposition to papillary thyroid cancer appears to consist of a variety of gene mutations that are mostly either of low penetrance and common or of high penetrance but rare. Moreover, they likely interact with each other and with environmental factors. The culpable genes may not be of the traditional, protein-coding type. A limited number of noncoding candidate genes have indeed been described, and we propose here that the failure to find mutations in traditional protein-coding genes is not coincidental. Instead, a more likely hypothesis is that changes in the expression of multiple regulatory RNA genes, e.g. microRNAs, may be a major mechanism. Our review of the literature strongly supports this notion in that a polymorphism in one microRNAs (miR-146a) predisposes to thyroid carcinoma, whereas numerous other microRNAs are involved in signaling (mainly PTEN/PI3K/AKT and T3/THRB) that is central to thyroid carcinogenesis.

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Figures

Fig. 1.

Fig. 1.

Regulation of PTEN/PI3K/AKT pathway by microRNAs. Arrows represent positive (green) or negative (red) regulation of the genes.

Fig. 2.

Fig. 2.

Target genes of microRNA deregulated in PTC tumors. The top seven microRNA up-regulated in PTC contain binding sites for the same one gene, namely THRB, as predicted by TargetScan software (P = 0.0000002). The size of every sector of the circle graph reflects the number of genes predicted to be regulated by a given microRNA. [Reproduced from K. Jazdzewski et al.: Thyroid hormone receptor β (THRB) is a major target gene for microRNAs deregulated in papillary thyroid carcinoma (PTC). J Clin Endocrinol Metab 96:E546–E553, 2011 (105), with permission. © The Endocrine Society.]

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