Essential Role of the 14q32 Encoded miRNAs in Endocrine Tumors.

Lilla Krokker,Henriett Butz,Attila Patócs

doi:10.3390/genes12050698

Lilla Krokker, Henriett Butz + Show 1 more

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https://doi.org/10.3390/genes12050698

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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.

Highlights

MicroRNAs are single-stranded, small (~17–22 nucleotide long), protein non-coding RNA molecules that regulate gene expression post-transcriptionally by RNA interference
Publication focused on 14q32 miRNAs regarding endocrine tumors, and high-throughput miRNA profiling studies of endocrine tumors were selected to construct an expression heatmap (Figure 1B, Table 1)
By using SNP array and DNA methylation analysis, this study identified LOH of chromosome arm 14q in all Mi1 adrenocortical carcinoma (ACC) tumors associated with Maternally Expressed Gene 3 (MEG3) promoter methylation

Summary

Introduction

MicroRNAs (miRNAs) are single-stranded, small (~17–22 nucleotide long), protein non-coding RNA molecules that regulate gene expression post-transcriptionally by RNA interference. According to the canonical miRNA biogenesis, the mature miRNA is generated from a hairpin RNA precursor molecule produced by RNA polymerase II or III [1]. The mature miRNA incorporates into a protein complex called miRISC (miRNA-induced silencing complex) [2]. In the miRISC complex miRNAs lead to translational repression, mRNA destabilization or mRNA cleavage through miRNA-mRNA interaction via base complementarity. MiRNAs target mRNAs mainly at 30 untranslated regions but even the coding sequence or 50 UTR have been described to be miRNA target regions [2]. It has been discovered that in some particular cases miRNAs can even enhance gene expression [2]. The 14q32 cluster is among the largest polycistronic miRNA clusters. miRNAs encoded here have been implicated in tumorigenesis of multiple organs including endocrine glands

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Conclusion