Essential Role of the 14q32 Encoded miRNAs in Endocrine Tumors

Abstract

Background: The 14q32 cluster is among the largest polycistronic miRNA clusters. miRNAs encoded here have been implicated in tumorigenesis of multiple organs including endocrine glands.

Methods: Critical review of miRNA studies performed in endocrine tumors have been performed. The potential relevance of 14q32 miRNAs through investigating their targets, and integrating the knowledge provided by literature data and bioinformatics predictions have been indicated.

Results: Pituitary adenoma, papillary thyroid cancer and a particular subset of pheochromocytoma and adrenocortical cancer are characterized by the downregulation of miRNAs encoded by the 14q32 cluster. Pancreas neuroendocrine tumors, most of the adrenocortical cancer and medullary thyroid cancer are particularly distinct, as 14q32 miRNAs were overexpressed. In pheochromocytoma and growth-hormone producing pituitary adenoma, however, both increased and decreased expression of 14q32 miRNAs cluster members were observed. In the background of this phenomenon methodological, technical and biological factors are hypothesized and discussed. The functions of 14q32 miRNAs were also revealed by bioinformatics and literature data mining.

Conclusions: 14q32 miRNAs have a significant role in the tumorigenesis of endocrine organs. Regarding their stable expression in the circulation of healthy individuals, further investigation of 14q32 miRNAs could provide a potential for use as biomarkers (diagnostic or prognostic) in endocrine neoplasms.

Keywords: 14q32; DLK1-MEG3 locus; adrenocortical cancer; endocrine tumor; miRNA; miRNA cluster; neuroendocrine tumor; pheochromocytoma; pituitary adenoma; thyroid cancer.

Figure 1

The imprinted 14q32 region. (A) On the paternal and maternal alleles middle: exons colored by grey indicate imprinted genes, exons colored by green indicate transcriptionally active state. DMR status is presented by grey (methylated) and white (unmethylated) circles. Black stripes represent imprinted miRNA genes, red stripes represent transcriptionally active miRNA genes. (B) On the heatmap (right): Representative expressional change of 14q32 miRNAs in endocrine tumors (downregulation and overexpression are presented compared to physiological, monoallelic expression. Heatmap was constructed using the data of 59 studies (see details in the methods section)). MiRNAs indicated on the heatmap are listed in Table 1 indicating the exact chromosomal localization. Colors indicate expression (blue color was used for low and red for high expression, grey represents monoallelic expression, white: no data available).