| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Moradi Sarabi, Mostafa Zahedi, Seyed Abdollah Pajouhi, Naser Khosravi, Peyman Bagheri, Shahrokh Ahmadvand, Hassan Shahryarhesami, Soroosh |
| Abstract | Background There is increasing evidence indicating an aberrant expression of miRNAs in colorectal cancer (CRC) development. Growing evidence has suggested that polyunsaturated fatty acids (PUFAs) could modulate the remodeling of the epigenome. No study has yet been published to examine the direct effect of PUFA on the promoter methylation of miRNAs. This study aimed to examine the potential clinical application of PUFA on the promoter DNA methylation of miR-126 and its angiogenic target molecule (VEGF) in the CRC cells. Methods We investigated the direct effect of 100 μM EPA, DHA, and LA for 24 h on promoter methylation status of miR-126 in a panel of five CRC cell lines (HCT116, HT29/219, Caco2, SW742, and LS180) by methylation-specific PCR (MSP). We also quantified the miR-126 and VEGF transcript expression levels in five CRC cell lines affected by PUFA by real-time PCR. Moreover, we analyzed the protein expression level of VEGF, as a target of miR-126, by western blotting assay. Results MSP analysis showed extensive DNA methylation of the miR-126 promoter in all five CRC cell lines, and among all three PUFAs, only DHA completely demethylated the promoter of miR-126 in HCT116 and Caco2 cell lines. We found that only DHA significantly induces the expression level of miR-126 in HCT116 and Caco2 cell lines, respectively, by 20.1-fold and 1.68-fold (p < 0.05). Our finding indicates that the downregulation of VEGF protein level is also effectively observed only in DHA-treated HCT116 and Caco2 cells compared to control cells (p < 0.05). Conclusions Our results provide evidence that n-3 PUFAs are able to modulate cellular miR-126 DNA methylation and inhibit VEGF expression level in a cell-type specific manner in colorectal cancer cells. DHA always showed higher efficacy than EPA and LA in our experiment. Overall, our results suggest a potential clinical application of n-3 PUFAs as anti-angiogenic agents in CRC therapy. |
| Related Links | https://genesandnutrition.biomedcentral.com/counter/pdf/10.1186/s12263-018-0623-5.pdf |
| Ending Page | 9 |
| Page Count | 9 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 18653499 |
| DOI | 10.1186/s12263-018-0623-5 |
| Journal | Genes & Nutrition |
| Issue Number | 1 |
| Volume Number | 13 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2018-12-18 |
| Access Restriction | Open |
| Subject Keyword | Human Genetics Clinical Nutrition Gene Function Biomedicine Colorectal cancer miRNA DNA methylation PUFA Protein expression |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism Genetics |
| Journal Impact Factor | 3.3/2023 |
| 5-Year Journal Impact Factor | 3.8/2023 |
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