Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 S1.1

ICEECE2012 Symposia Molecular mechanisms of differentiated thyroid cancer (3 abstracts)

Molecular consequences of deregulated RNA genes in papillary thyroid carcinoma

A. de la Chapelle 1,

1Ohio State University, Columbus, Ohio, USA; 2The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.

Early miR expression analyses in papillary thyroid carcinoma (PTC) disclosed profound differences in the expression of several, microRNAs in thyroid tumor compared with unaffected thyroid tissue. For instance, miR146 and miR221 were 19- and 11-fold upregulated in PTC. These and other miRs target the thyroid hormone receptor THRB gene. Transfection of cell lines with miR146a and other miRs in vitro resulted in down-regulation of THRB transcript and protein. Promoter luciferase reporter experiments as well as in vivo measurements were concordant. These findings are reflected in vivo in thyroid tumor tissue (miRs are up, THRB is down). Thus miRs up-regulated in PTC tumors directly inhibit the expression of THRB, an important tumor suppressor gene.

Examples from other cancers suggest that many more miRs are probably involved in PTC pathogenesis. Indeed the early studies targeted only a fraction (n=460) of all miRs known today (n>1500). All miRs in the genome can presently be assessed by RNA sequencing. Such studies are in progress and may reveal roles for miR-mediated perturbations in key PTC pathways but definitive data are not presently available.

Recent advances fueled by second-generation deep sequencing implicate long intergenic noncoding RNAs (lincRNAs) in the pathogenesis of cancer. Examples in thyroid pathology include the NAMA gene in 9q22. NAMA is a noncoding RNA associated with the MAP kinase pathway and growth arrest. The PTCSC1 gene in 8q24 is embedded in the introns of two protein-coding genes, thyroglobulin (TG) and Src-like adaptor (SLA). The PTCSC3 gene in 14q13 is a highly thyroid-specific spliced gene that is strongly downregulated in PTC tumors. By functional assays it acts as a tumor suppressor. Some unpublished data on lincRNA genes will be discussed.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

Browse other volumes

Article tools

My recent searches

No recent searches.