Folic Acid Supplementation Promotes Hypomethylation in Both the Inflamed Colonic Mucosa and Colitis-Associated Dysplasia
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Diet and Animal Treatment
2.2. Histopathology
2.3. Isolation of DNA and RNA from Laser Microdissected (LMD) Colonic Epithelial Cells
2.4. Genome-Wide CpG island Methylation Analysis
2.5. RNA-Seq Analysis
2.6. Immunohistochemistry (IHC) of β-Catenin
2.7. Real-Time Quantitative PCR (RT-qPCR)
2.8. Biostatistical Analyses
3. Results
3.1. Treatment Tolerance
3.2. Effect of FA on the Development of Colitis-Associated Dysplasia and Cancer
3.3. Effect of FA on Genome-Wide DNA Methylation at CCCGGG Sites
3.4. Expression of Genes whose Methylation Status was Modified by FA Treatment
3.5. Effect of FA on Inflammatory Markers
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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A | B | C | D | E | F |
---|---|---|---|---|---|
Gene | ND ** FA 8 mg/0 mg | Polyp ζ FA 8 mg/0 mg | 8 mg FA Polyp/ND | 0 mg FA Polyp/ND | Signaling pathways and/or cellular function |
Tbxt (T, Brachyury) | 11.8 | 0.9 | 4.7 | 61.4 | Wnt target gene [32,33] |
Slc4a11 | 3.1 | 1.0 | 3.2 | 10.5 | H+(OH×) and NH3-H+ transporter protein; [34] necessary for cell survival [35] |
Dusp4 (Mkp-2) | 2.1 | 1.4 | 4.7 | 7.0 | Negative regulator of MAPK, overexpressed in CRC [36,37] |
Spink4 | 2.1 | 1.1 | 0.5 | 0.9 | Marker for intestinal goblet cells, downregulated in CRC [38,39] |
Thbs1 (Tsp1) | 1.7 | 1.1 | 2.9 | 4.6 | Negative regulator of angiogenesis; [40] increased expression in inflammatory bowel disease [41] |
Epha2 | 1.8 | 0.9 | 2.1 | 4.1 | Effector of MAPK signaling and overexpressed in CRC [42,43] |
Zfp703 | 1.7 | 1.3 | 1.5 | 2.0 | Wnt target gene [44] |
Enc1 | 1.4 | 1.2 | 2.1 | 2.4 | Wnt target gene [45] |
Atp11a | 1.3 | 1.3 | 2.8 | 2.6 | ATPase with higher expression in CRC [46] |
Lzts1 (Fez1) | 0.8 | 0.8 | 2.0 | 2.1 | Tumor suppressor gene; regulates M phase during cell cycle [47,48] |
Tns4 (Cten) | 0.6 | 1.2 | 2.6 | 1.2 | Interacts with β-catenin; overexpressed in CRC [49] |
Neu1 | 0.6 | 1.1 | 0.8 | 0.4 | Inhibits β-catenin expression [50] |
Rab11fip4 | 0.6 | 0.9 | 0.5 | 0.3 | HIF-1α target gene and effector of RAB11 [39] |
Rims4 | 0.5 | 0.3 | 0.2 | 0.1 | Maintains Ca2+ influx [51] |
Fut9 | 0.3 | 1.1 | 0.8 | 0.3 | Essential in tumor-initiating cells; switched off to enhance the aggressiveness of tumor cells [52] |
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Chang, W.-C.L.; Ghosh, J.; Cooper, H.S.; Vanderveer, L.; Schultz, B.; Zhou, Y.; Harvey, K.N.; Kaunga, E.; Devarajan, K.; Li, Y.; et al. Folic Acid Supplementation Promotes Hypomethylation in Both the Inflamed Colonic Mucosa and Colitis-Associated Dysplasia. Cancers 2023, 15, 2949. https://doi.org/10.3390/cancers15112949
Chang W-CL, Ghosh J, Cooper HS, Vanderveer L, Schultz B, Zhou Y, Harvey KN, Kaunga E, Devarajan K, Li Y, et al. Folic Acid Supplementation Promotes Hypomethylation in Both the Inflamed Colonic Mucosa and Colitis-Associated Dysplasia. Cancers. 2023; 15(11):2949. https://doi.org/10.3390/cancers15112949
Chicago/Turabian StyleChang, Wen-Chi L., Jayashri Ghosh, Harry S. Cooper, Lisa Vanderveer, Bryant Schultz, Yan Zhou, Kristen N. Harvey, Esther Kaunga, Karthik Devarajan, Yuesheng Li, and et al. 2023. "Folic Acid Supplementation Promotes Hypomethylation in Both the Inflamed Colonic Mucosa and Colitis-Associated Dysplasia" Cancers 15, no. 11: 2949. https://doi.org/10.3390/cancers15112949