Related Experiment Video
Updated: May 24, 2025

Sample Preparation to Bioinformatics Analysis of DNA Methylation: Association Strategy for Obesity and Related Trait Studies
Published on: May 6, 2022
Dietary polyunsaturated fatty acids affect PPARγ promoter methylation status and regulate the PPARγ/COX2 pathway in
Esmaeel Babaeenezhad1,2,3, Peyman Khosravi1,2,3, Mostafa Moradi Sarabi4,5
1Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
Background:
Promoter methylation silencing of peroxisome proliferator-activated receptor gamma (PPARγ) and dysregulation of the PPARγ/COX2 axis contribute to colorectal cancer (CRC) pathogenesis. This study investigated for the first time the effects of dietary polyunsaturated fatty acids (PUFAs) on promoter methylation of PPARγ and the PPARγ/COX2 axis in five CRC cell lines.
Methods:
Five CRC cell lines (SW742, HCT116, Caco2, LS180, and HT29/219) were treated with 100 µM of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) or linoleic acid (LA). The methylation patterns of the four regions within the PPARγ promoter were determined using methylation-specific PCR (MSP). Additionally, the mRNA expression levels of PPARγ and COX2 were examined using RT-qPCR.
Results:
Our results showed that M3 segment within the PPARγ promoter was hemimethylated in SW742 cells, whereas other cell lines remained unmethylated in this region. The M4 region was hemimethylated in all the CRC cell lines. Of all PUFAs, DHA demethylated the M3 region of the PPARγ promoter in SW742 cells and the M4 region in Caco2 cells. Functionally, these changes were accompanied by significant upregulation of PPARγ in SW742 (9.22-fold; p = 0.01) and Caco2 cells (8.87-fold; p = 0.04). Additionally, COX2 expression was significantly downregulated in all CRC cell lines after exposure to PUFAs (p < 0.05).
Conclusions:
This study demonstrated that PUFAs, particularly DHA, altered PPARγ promoter methylation and expression, as well as modulated the PPARγ/COX2 axis in CRC cells in a cell type-dependent manner. DHA was more effective than the other PUFAs in regulating PPARγ promoter methylation. Our results highlight the potential clinical use of PUFAs in CRC treatment.
Related Concept Videos
Epigenetic Regulation
X-chromosome...
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Abnormal Proliferation
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
Co-activators and Co-repressors
Cell Specific Gene Expression

