Epigenetic mechanisms of transcriptional regulation of 14q32 region in thyroid papillary carcinoma

Abstract

The knowledge obtained in the past few years concerning non-coding RNAs (ncRNAs) has changed majorly our perception about their role in cell biology. Thought to be part of what was once called "junk transcripts", ncRNAs have revealed to play important regulatory functions within cells, mediating all cellular processes. The human chromosome 14 bears several ncRNA genes, including one of the largest microRNA (miRNA) clusters within the genome, the DLK1-DIO3 cluster, comprising more than 50 miRNAs genes. MiRNAs are small ncRNA molecules that play an important role in post-transcriptional regulation in several physiological and pathological processes. The expression of miRNAs from the DLK1-DIO3 genomic region has been shown to be globally decreased in papillary thyroid carcinoma (PTC), however the mechanisms underlying this phenomenon lacks elucidation. In this study we aim to characterize the epigenetic mechanisms that control the 14q32 region both in healthy thyroid cells and PTC cells by investigating lncRNAs which potentially interact with the region and the region's methylation and histone modification patterns. This knowledge will certainly contribute to elucidate how epigenetic mechanisms acting in the control of the region's expression influence in PTC's genesis and progression. (AU)