Epigenetic Regulation of DLK1-DIO3 Region in Thyroid Carcinoma
Alves, Leticia F. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
da Silva, Isabelle N. (University of Campinas)
de Mello, Diego Claro (University of Sao Paulo)
Fuziwara, Cesar S. (University of Sao Paulo)
Guil, Sonia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Geraldo, Murilo (University of Campinas)

Data:	2024
Resum:	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.
Ajuts:	Agencia Estatal de Investigación PID2019-111658RB-I00
Nota:	Altres ajuts: Sao Paulo Research (grants: LFA 2017/21660-0 and 2020/02440-1; MVG 2017/03635-8; CSF 2019/17282-5)
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Thyroid cancer ; Epigenetics ; Methylation ; NcRNAs
Publicat a:	Cells, Vol. 13 Núm. 12 (June 2024) , ISSN 2073-4409

DOI: 10.3390/cells13121001
PMID: 38920632

13 p, 2.5 MB

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