Identification of microRNAs in the Intergenic Regions of BRAF Genes

In Papillary Thyroid Carcinoma (PTC), the BRAFV600E mutation represents 90% of cases, considered a point mutation due to the transversion of thymine (T1799A) of the BRAF gene by replacing valine with glutamate (V600E), in the serine/threonine kinase chain. It activates the recruitment of RAF proteins (BRAF in thyroid follicular cells) to the plasma membrane, activating ERK kinase (MEK), which phosphorylates and activates the extracellular signal-regulated kinase (ERK). In the nucleus, ERK regulates transcription genes involved in cell differentiation, proliferation, and survival. In the human genome, the evidence of microRNAs in regions favorable to carcinogenesis is 50%. MicroRNAs (small non-coding RNAs) act in post-transcriptional regulation, causing inhibition of translation or degradation of mRNAs, whose altered expression is evidenced in papillary thyroid carcinoma (for example, miR-146, miR-222, and miR-221). We identified 9 families of small RNAs in the intronic regions of the BRAF gene: BRAF-207, BRAF-208, BRAF-209, BRAF-211, BRAF-212, BRAF-214, BRAF-216, BRAF-217, and BRAF-218. Among the non-protein-coding BRAF gene intronic transcripts, we determined putative targets for microRNA signatures mir-1255, mir-562, mir-544, and mir-574. An mRNA target of mir-562 is the EIF1AX gene, recently described as a new gene related to thyroid cancer. The results provide a better understanding of the participation of this type of RNA in post-transcriptional regulation in thyroid cancer, representing an accessible and differentiated molecular methodological development, thus contributing to therapeutic decisions in cases of indeterminate thyroid nodules.