Lipids & metabolic liver disease
Epigenetic regulation of thyroid hormone action in human metabolic dysfunction-associated steatohepatitis
Authors' conclusion
miR-34a-5p constitutes a possible epigenetic master regulator of hepatic TH action, which together with THRB-specific DNA methylation could explain a possible developing TH resistance in the liver during MASH progression on the molecular level.
Study context
- Population
- Liver samples from patients with and without MASH; HepG2 cells
- Comparison
- Liver samples from patients with vs without MASH; miR-34a-5p overexpression in HepG2 cells
- Outcome
- Epigenetic regulation of hepatic thyroid hormone (TH) action
Methodological detailsqRT-PCR of liver samples correlated with clinical parameters; luciferase reporter assays and miRNA overexpression in HepG2 cells; DNA methylation by bisulfite pyrosequencing
- qRT-PCR of liver samples correlated with clinical parameters; luciferase reporter assays and miRNA overexpression in HepG2 cells; DNA methylation by bisulfite pyrosequencing
Main finding
As reported in the abstract
- miR-34a-5p upregulated in MASH patients and correlated positively with clinical parameters of MASH
- Functional binding of miR-34a-5p to seed sequence in TH receptor beta (THRB) and DIO1 genes
- miR-34a-5p overexpression in HepG2 cells reduced expression of THRA, THRB, DIO1 and SLC10A1
- DNA methylation of THRB intron 1 increased in MASH and negatively correlated with THRB expression
Original publication
Epigenetic regulation of thyroid hormone action in human metabolic dysfunction-associated steatohepatitis. Eur Thyroid J. Published 21 September 2024. doi:10.
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