Non-coding RNAs (ncRNAs) have emerged as pivotal regulators in cellular biology, dispelling their former perception as ‘junk transcripts’. Notably, the DLK1-DIO3 region harbors numerous ncRNAs, including long non-coding RNAs (lncRNAs) and over 50 microRNA genes. While papillary thyroid cancer showcases a pervasive decrease in DLK1-DIO3-derived ncRNA expression, the precise mechanisms driving this alteration remain elusive. We hypothesized that epigenetic alterations underlie shifts in ncRNA expression during thyroid cancer initiation and progression. This study aimed to elucidate the epigenetic mechanisms governing DLK1-DIO3 region expression in this malignancy. We have combined the analysis of DNA methylation by bisulfite sequencing together with that of histone modifications through ChIP-qPCR to gain insights into the epigenetic contribution to thyroid cancer in cell lines representing malignancies with different genetic backgrounds. Our findings characterize the region’s epigenetic signature in thyroid cancer, uncovering distinctive DNA methylation patterns, particularly within CpG islands on the lncRNA MEG3-DMR, which potentially account for its downregulation in tumors. Pharmacological intervention targeting DNA methylation combined with histone deacetylation restored ncRNA expression. These results contribute to the understanding of the epigenetic mechanisms controlling the DLK1-DIO3 region in thyroid cancer, highlighting the combined role of DNA methylation and histone marks in regulating the locus’ expression.

In the present study, we characterized and investigated the effect of the araçá-boi extract on antioxidant activity, cell viability, and the regulation of genes related to tumor suppression and epigenetic mechanisms in ovarian cancer cells. The results showed that araçá-boi extract revealed a remarkable diversity of phytochemicals (organic acids, phenolic acids, and flavonoids), significant antioxidant potential, and efficient scavenging of reactive oxygen species, particularly hydroxyl and peroxyl radicals. Gallic acid, one of the phenolic acids present in the extract, was used alone to verify its contribution to cytotoxic activities. Exposure of human ovarian cancer cells (NCI/ADR-RES and OVCAR3) to the extract (0.15–150 μg/mL) and gallic acid (6–48 μg/mL) resulted in a significant reduction in cell viability, particularly after 48 h of treatment. Both treatments modulated genes involved in DNA repair, tumor suppression, and epigenetic regulation. However, no changes were observed in the methylation status of the BRCA1 gene promoter region with either araçá-boi extract or gallic acid. These findings reinforce the therapeutic potential of araçá-boi extract and its phenolic compounds against ovarian cancer and point to the need for further studies to better elucidate the molecular pathways involved and validate these effects in vivo.