Epigenetic Regulation of DLK1-DIO3 Region in Thyroid Carcinoma.
Cells
; 13(12)2024 Jun 08.
Article
in En
| MEDLINE
| ID: mdl-38920632
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium-Binding Proteins
/
Thyroid Neoplasms
/
Gene Expression Regulation, Neoplastic
/
DNA Methylation
/
Epigenesis, Genetic
/
RNA, Long Noncoding
/
Iodide Peroxidase
Limits:
Humans
Language:
En
Journal:
Cells
Year:
2024
Document type:
Article
Affiliation country:
España