Changes in Methylation across Structural and MicroRNA Genes Relevant for Progression and Metastasis in Colorectal Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Tissue Material and Ethical Consent
2.2. Genomic DNA Isolation
2.3. Methylation Profiling
2.4. Bioinformatics Analysis
2.5. Data Availability
2.6. KEGG Analysis
2.7. Ingenuity Pathway Analysis (IPA)
3. Results
3.1. Methylation Array and Associated Bioinformatics: General Distribution of Differentially Methylated Sites between Coding, Non-Coding, and Intergenic Regions
3.2. Hypermethylated and Hypomethylated CpG Areas across Genomic Features
3.3. Methylation-Specific Patterns across miR Genes
3.4. Identification of Significant Differentially Methylated miRs
3.5. Pathway Enrichment Analysis of Differentially Methylated miR Genes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chromosome (Chr) | Status | OpenSea | Island | Shelf | Shore |
---|---|---|---|---|---|
Chr1 | Hypomethylated | 786 | 39 | 142 | 179 |
Hypermethylated | 57 | 636 | 10 | 210 | |
Chr2 | Hypomethylated | 861 | 40 | 137 | 168 |
Hypermethylated | 36 | 568 | 5 | 154 | |
Chr3 | Hypomethylated | 532 | 17 | 73 | 70 |
Hypermethylated | 30 | 430 | 15 | 155 | |
Chr4 | Hypomethylated | 442 | 5 | 83 | 85 |
Hypermethylated | 12 | 462 | 7 | 120 | |
Chr5 | Hypomethylated | 588 | 28 | 91 | 118 |
Hypermethylated | 62 | 541 | 4 | 116 | |
Chr6 | Hypomethylated | 781 | 13 | 96 | 111 |
Hypermethylated | 75 | 503 | 17 | 201 | |
Chr7 | Hypomethylated | 728 | 55 | 151 | 195 |
Hypermethylated | 50 | 533 | 21 | 162 | |
Chr8 | Hypomethylated | 597 | 29 | 93 | 142 |
Hypermethylated | 26 | 502 | 7 | 164 | |
Chr9 | Hypomethylated | 106 | 13 | 26 | 69 |
Hypermethylated | 12 | 177 | 5 | 28 | |
Chr10 | Hypomethylated | 506 | 26 | 101 | 121 |
Hypermethylated | 40 | 573 | 5 | 116 | |
Chr11 | Hypomethylated | 686 | 19 | 84 | 131 |
Hypermethylated | 41 | 448 | 4 | 147 | |
Chr12 | Hypomethylated | 485 | 18 | 78 | 115 |
Hypermethylated | 43 | 357 | 20 | 109 | |
Chr13 | Hypomethylated | 517 | 17 | 85 | 97 |
Hypermethylated | 29 | 372 | 11 | 170 | |
Chr14 | Hypomethylated | 253 | 9 | 39 | 58 |
Hypermethylated | 13 | 220 | 5 | 74 | |
Chr15 | Hypomethylated | 313 | 9 | 35 | 39 |
Hypermethylated | 9 | 219 | 4 | 34 | |
Chr16 | Hypomethylated | 267 | 29 | 68 | 121 |
Hypermethylated | 35 | 295 | 15 | 59 | |
Chr17 | Hypomethylated | 242 | 7 | 75 | 80 |
Hypermethylated | 27 | 229 | 4 | 46 | |
Chr18 | Hypomethylated | 37 | 14 | 33 | 27 |
Hypermethylated | 1 | 161 | 4 | 22 | |
Chr19 | Hypomethylated | 262 | 40 | 114 | 119 |
Hypermethylated | 37 | 524 | 18 | 147 | |
Chr20 | Hypomethylated | 223 | 41 | 88 | 127 |
Hypermethylated | 2 | 385 | 5 | 85 | |
Chr21 | Hypomethylated | 67 | 4 | 18 | 23 |
Hypermethylated | 5 | 88 | 0 | 20 | |
Chr22 | Hypomethylated | 63 | 23 | 37 | 49 |
Hypermethylated | 1 | 98 | 3 | 21 |
Chromosome | Status | OpenSea | Island | Shelf | Shore |
---|---|---|---|---|---|
Chr1 | Hypomethylated | 5 | 0 | 0 | 0 |
Hypermethylated | 0 | 1 | 0 | 2 | |
Chr2 | Hypomethylated | 1 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr3 | Hypomethylated | 6 | 0 | 0 | 0 |
Hypermethylated | 1 | 1 | 0 | 0 | |
Chr4 | Hypomethylated | 0 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr5 | Hypomethylated | 1 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr6 | Hypomethylated | 5 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr7 | Hypomethylated | 12 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr8 | Hypomethylated | 1 | 0 | 0 | 1 |
Hypermethylated | 0 | 3 | 0 | 7 | |
Chr9 | Hypomethylated | 1 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr10 | Hypomethylated | 0 | 1 | 3 | 2 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr11 | Hypomethylated | 2 | 0 | 0 | 0 |
Hypermethylated | 2 | 12 | 0 | 0 | |
Chr12 | Hypomethylated | 0 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr13 | Hypomethylated | 12 | 0 | 3 | 1 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr14 | Hypomethylated | 25 | 1 | 1 | 2 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Chr15 | Hypomethylated | 1 | 1 | 0 | 1 |
Hypermethylated | 0 | 5 | 0 | 0 | |
Chr16 | Hypomethylated | 1 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 1 | |
Chr17 | Hypomethylated | 0 | 0 | 0 | 0 |
Hypermethylated | 0 | 0 | 0 | 0 | |
Hypomethylated | 0 | 0 | 0 | 0 | |
Chr18 | Hypermethylated | 0 | 0 | 0 | |
Hypomethylated | 20 | 0 | 0 | 0 | |
Chr19 | Hypermethylated | 0 | 0 | 0 | 0 |
Hypomethylated | 5 | 0 | 0 | 0 | |
Chr20 | Hypermethylated | 0 | 18 | 0 | 1 |
Hypomethylated | 0 | 0 | 0 | 0 | |
Chr21 | Hypermethylated | 0 | 0 | 0 | 0 |
Hypomethylated | 0 | 0 | 0 | 0 | |
Chr22 | Hypermethylated | 1 | 0 | 0 | 0 |
Hypermethylated miRs Found in Our Study | miR Expression in Cancer | Regulation | Role | Cancer Types | Target Genes | References |
---|---|---|---|---|---|---|
hsa-miR-124-2 | Downregulated | Hypermethylated | Tumor suppressor | Cervical cancer | IGFBP7 | [30] |
hsa-miR-124-3 | Downregulated | Hypermethylated | Tumor suppressor | Prostate cancer, Cervical cancer, HCC, Bladder cancer, CRC | IGFBP7, CRKL, Sp1, EDNRB, CCL20, DNMT3B, STAT3 | [30,31,32,33,34,35,36,37] |
hsa-miR-129-2 | Downregulated | Hypermethylated | Tumor suppressor | Esophageal carcinoma, Breast cancer, CRC | SOX4, BCL2L2, BCL2 | [38,39,40] |
hsa-miR-137 | Downregulated | Hypermethylated | Tumor suppressor | Endometrial cancer, CRC, Pancreatic cancer | EZH2, LSD1, TCF4, LSD1, KLF12, KDM4A | [14,41,42,43,44,45] |
hsa-miR-34B | Downregulated | Hypermethylated | Tumor suppressor | Cervical cancer, Lung adenocarcinoma, Breast cancer, Oropharyngeal (oral) cancer, NSCLC | TGF-β1, BMF, Cyclin D1, JAG1 | [46,47,48,49,50,51] |
hsa-miR-34C | Downregulated | Hyper- methylated | Tumor suppressor | Nasopharyngeal carcinoma, Prostate cancer | MET | [52,53] |
hsa-miR-34b/c | Downregulated | Hypermethylated | Tumor suppressor | CRC | - | [54] |
hsa-miR-762 | Upregulated | - | Tumor promoter | Breast cancer | IRF7 | [55] |
hsa-miR-9-3 | Downregulated | Hypermethylated | Tumor suppressor | Hodgkin’s lymphoma, Gastric cancer | ITGB1 | [56,57] |
Hypomethylated miRs Found in Our Study | miR Expression in Cancer | Regulation | Role | Cancer Types | Target Genes | References |
hsa-miR-1204 | Upregulated | - | Tumor promoter | Breast cancer, Glioblastoma | VDR, CREB-1 | [58,59] |
hsa-miR-17 | Upregulated | - | Tumor promoter | CRC | - | [60] |
hsa-miR-18A | Upregulated | - | Tumor promoter | Prostate cancer, Breast cancers, Osteosarcoma, Nasopharyngeal carcinoma, CRC | STK4, IRF2, Dicer1 | [14,61,62,63,64] |
hsa-miR-19A | Upregulated | - | Tumor promoter | CRC, Gastric cancer, HCC | TIA1, MXD1, PTEN | [14,65,66,67,68] |
hsa-miR-19B1 | Upregulated | - | Tumor promoter | Gastric cancer | MXD1 | [67] |
hsa-miR-20A | Upregulated | - | Tumor promoter | CRC | WTX | [69] |
hsa-miR-548F5 | - | Hyper- methylated | - | Schwannomas | - | [70] |
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Share and Cite
Patil, N.; Abba, M.L.; Zhou, C.; Chang, S.; Gaiser, T.; Leupold, J.H.; Allgayer, H. Changes in Methylation across Structural and MicroRNA Genes Relevant for Progression and Metastasis in Colorectal Cancer. Cancers 2021, 13, 5951. https://doi.org/10.3390/cancers13235951
Patil N, Abba ML, Zhou C, Chang S, Gaiser T, Leupold JH, Allgayer H. Changes in Methylation across Structural and MicroRNA Genes Relevant for Progression and Metastasis in Colorectal Cancer. Cancers. 2021; 13(23):5951. https://doi.org/10.3390/cancers13235951
Chicago/Turabian StylePatil, Nitin, Mohammed L. Abba, Chan Zhou, Shujian Chang, Timo Gaiser, Jörg H. Leupold, and Heike Allgayer. 2021. "Changes in Methylation across Structural and MicroRNA Genes Relevant for Progression and Metastasis in Colorectal Cancer" Cancers 13, no. 23: 5951. https://doi.org/10.3390/cancers13235951