Expression and Prognostic Value of m6A RNA Methylation-Related Genes in Thyroid Cancer
Background: N6-methyladenosine (m6A) methylation modification is involved in tumorigenesis and progression and can affect various stages of RNA processing. We aimed to determine m6A methylation modifications on a transcriptome-wide scale in thyroid cancer.
Methods: RNA samples from cancerous tissues and adjacent tissues extracted from patients with papillary thyroid carcinoma (PTC) from Hangzhou First People’s Hospital, Zhejiang, China from January 2019 to January 2020 were used for m6A-sequencing. The biological function of differentially expressed genes (DEGs) was analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Correlation analysis between the results of transcriptome sequencing and m6A-sequencing was also performed. The key m6A immune-related genes were downloaded from Immport. LASSO regression was performed on the resulting genes to establish a prognostic risk model, which was verified by multivariate Cox proportional hazards regression analyses, receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis.
Results: An increase in m6A content in the total RNA of PTC was observed. A total of 123 genes with significant differential expression and differential methylation sites in thyroid cancer were selected, related to protein digestion and absorption, linoleic acid metabolism, legionellosis and alpha-linolenic acid metabolism. Seven genes (GDNF, EBI3, CCL2, BMP5, TGFB2, CGB3 and RLN2) were found to be predictive of PTC.
Conclusion: We analyzed the expression, enrichment pathways and functions of m6A methylation-related genes in the whole transcriptome of thyroid cancer and provided a prognostic risk model for thyroid cancer patients.
2. Zhou Z, Liu H, Yang Y, et al (2022). The five major autoimmune diseases increase the risk of cancer: epidemiological data from a large-scale cohort study in China. Cancer Commun (Lond), 42(5):435-446.
3. Jillard CL, Scheri RP, Sosa JA (2015). What Is the Optimal Treatment of Papillary Thyroid Cancer? Adv Surg, 49:79-93.
4. McLeod DS, Sawka AM, Cooper DS (2013). Controversies in primary treatment of low-risk papillary thyroid cancer. Lancet, 381(9871):1046-57.
5. Zhu W, Wang JZ, Xu Z, et al (2019). Detection of N6‑methyladenosine modification residues (Review). Int J Mol Med, 43(6):2267-2278.
6. Meyer KD, Jaffrey SR (2017). Rethinking m(6)A Readers, Writers, and Erasers. Annu Rev Cell Dev Biol, 33:319-342.
7. He L, Li H, Wu A, Peng Y, Shu G, Yin G (2019). Functions of N6-methyladenosine and its role in cancer. Mol Cancer, 18(1):176.
8. Sun T, Wu R, Ming L (2019). The role of m6A RNA methylation in cancer. Biomed Pharmacother, 112:108613.
9. Xiang M, Liu W, Tian W, You A, Deng D (2020). RNA N-6-methyladenosine enzymes and resistance of cancer cells to chemotherapy and radiotherapy. Epigenomics, 12(9):801-809.
10. Chen X, Xu M, Xu X, et al (2022). METTL14 Suppresses CRC Progression via Regulating N6-Methyladenosine-Dependent Primary miR-375 Processing. Mol Ther, 28(2):599-612.
11. Dominissini D, Moshitch-Moshkovitz S, Schwartz S, et al (2012). Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature, 485(7397):201-6.
12. Lee JM, Lee H, Kang S, Park WJ (2016). Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances. Nutrients, 8(1):23.
13. Massey KA, Nicolaou A (2011). Lipidomics of polyunsaturated-fatty-acid-derived oxygenated metabolites. Biochem Soc Trans, 39(5):1240-6.
14. Gorjao R, Dos Santos CMM, Serdan TDA, et al (2019). New insights on the regulation of cancer cachexia by N-3 polyunsaturated fatty acids. Pharmacol Ther, 196:117-134.
15. Huang M, Narita S, Koizumi A, et al (2021). Macrophage inhibitory cytokine-1 induced by a high-fat diet promotes prostate cancer progression by stimulating tumor-promoting cytokine production from tumor stromal cells. Cancer Commun (Lond), 41(5):389-403.
16. Zhang M, Yang F Jr, Yang F, et al (2009). Cytotoxic aggregates of alpha-lactalbumin induced by unsaturated fatty acid induce apoptosis in tumor cells. Chem Biol Interact, 180(2):131-42.
17. Kim KM, Jung BH, Lho DS, et al (2003). Alteration of urinary profiles of endogenous steroids and polyunsaturated fatty acids in thyroid cancer. Cancer Lett, 202(2):173-9.
18. Shi ZJ, Zhou HX, Pan B, et al (2017). Exploring the key genes and pathways of osteosarcoma with pulmonary metastasis using a gene expression microarray. Mol Med Rep, 16(5):7423-7431.
19. Dong LF, Xu SY, Long JP, Wan F, Chen YD (2017). RNA-Sequence Analysis Reveals Differentially Expressed Genes (DEGs) in Patients Exhibiting Different Risks of Tumor Metastasis. Med Sci Monit, 23:2842-2849.
20. Hsu LI, Briggs F, Shao X, et al (2016). Pathway Analysis of Genome-wide Association Study in Childhood Leukemia among Hispanics. Cancer Epidemiol Biomarkers Prev, 25(5):815-22.
21. Mulligan LM (2019). GDNF and the RET Receptor in Cancer: New Insights and Therapeutic Potential. Front Physiol, 9:1873.
22. Michaud D, Mirlekar B, Bischoff S, et al (2020). Pancreatic cancer-associated inflammation drives dynamic regulation of p35 and Ebi3. Cytokine, 125:154817.
23. Faustino LD, Griffith JW, Rahimi RA, et al (2020). Interleukin-33 activates regulatory T cells to suppress innate γδ T cell responses in the lung. Nat Immunol, 21(11):1371-1383.
24. Tanaka K, Kurebayashi J, Sohda M, et al (2009). The expression of monocyte chemotactic protein-1 in papillary thyroid carcinoma is correlated with lymph node metastasis and tumor recurrence. Thyroid, 19(1):21-5.
25. Houtman E, Tuerlings M, Suchiman HED, et al (2022). Inhibiting thyroid activation in aged human explants prevents mechanical induced detrimental signalling by mitigating metabolic processes. Rheumatology (Oxford), 62(1):457-466.
26. Song C, Zhou C (2021). HOXA10 mediates epithelial-mesenchymal transition to promote gastric cancer metastasis partly via modulation of TGFB2/Smad/METTL3 signaling axis. J Exp Clin Cancer Res, 40(1):62.
27. Śliwa A, Kubiczak M, Szczerba A, et al (2019). Regulation of human chorionic gonadotropin beta subunit expression in ovarian cancer. BMC Cancer, 19(1):746.
28. Singh P, Chalertpet K, Sukbhattee J, et al (2022). Association between promoter methylation and gene expression of CGB3 and NOP56 in HPV-infected cervical cancer cells. Biomed Rep,16(1):1.
29. Bialek J, Kunanuvat U, Hombach-Klonisch S, et al (2011). Relaxin enhances the collagenolytic activity and in vitro invasiveness by upregulating matrix metalloproteinases in human thyroid carcinoma cells. Mol Cancer Res, 9(6):673-87.
|Issue||Vol 52 No 9 (2023)|
|Thyroid cancer N6-methyladenosine Methylated RNA immunoprecipitation sequencing|
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