nach oben

Inflammation Research

Erschienen in:

27.10.2023 | Original Research Paper

Identification of novel N7-methylguanine-related gene signatures associated with ulcerative colitis and the association with biological therapy

verfasst von: Lichao Yang, Lianwen Yuan

Erschienen in: Inflammation Research | Ausgabe 12/2023

Einloggen, um Zugang zu erhalten

Abstract

Objective

Ulcerative colitis (UC) is an inflammatory disease characterized by recurrent episodes of chronic intestinal inflammation. It is closely associated with immune dysregulation in the intestines. However, the mechanisms underlying the role of immune-related N7-methylguanosine (m7G) internal modification in UC remain unclear.

Methods

We conducted a screening of differentially expressed genes (DEGs) associated with m7G and performed immune infiltration analysis. We then investigated the correlation between m7G-related DEGs and immune cells or pathways. To further explore the functional implications, we conducted functional enrichment analysis to identify gene modules that strongly correlated with hub gene expression. In addition, we constructed a miRNA regulatory network for the hub genes in UC. Furthermore, we examined the association between hub genes and disease remission in UC patients undergoing biologic therapy.

Results

We obtained 13 m7G-related DEGs and conducted an in-depth analysis of immune infiltration. Among them, we identified five hub genes (NUDT7, NUDT12, POLR2H, QKI, and PRKCB) that showed diagnostic potential for UC. Through WGCNA and KEGG analysis, we found that gene modules strongly correlated with m7G hub gene expression were enriched in inflammation-related pathways. Furthermore, Kaplan–Meier survival analysis revealed a significant association between changes in hub gene expression levels and disease remission in UC patients undergoing biologic therapy.

Conclusion

The findings of this study demonstrate that five m7G-related DEGs, including the m7G-modified recognition protein QKI, play a key role in the occurrence and progression of UC intestinal inflammation, which is closely related to intestinal immunity. These results provide valuable insights into the mechanisms of m7G modification in UC development and offer new perspectives for exploring novel therapeutic targets for UC.

Nur mit Berechtigung zugänglich

Conrad K, Roggenbuck D, Laass MW. Diagnosis and classification of ulcerative colitis. Autoimmun Rev. 2014;13:463–6. https://doi.org/10.1016/j.autrev.2014.01.028.CrossRefPubMed

Christensen B, Hanauer SB, Erlich J, Kassim O, Gibson PR, Turner JR, Hart J, Rubin DT. Histologic normalization occurs in ulcerative colitis and is associated with improved clinical outcomes. Clin Gastroenterol Hepatol. 2017;15:1557-1564.e1. https://doi.org/10.1016/j.cgh.2017.02.016.CrossRefPubMedCentralPubMed

Luo H, Cao G, Luo C, Tan D, Vong CT, Xu Y, Wang S, Lu H, Wang Y, Jing W. Emerging pharmacotherapy for inflammatory bowel diseases. Pharmacol Res. 2022;178: 106146. https://doi.org/10.1016/j.phrs.2022.106146.CrossRefPubMed

de Souza HSP, Fiocchi C. Immunopathogenesis of IBD: current state of the art. Nat Rev Gastroenterol Hepatol. 2016;13:13–27. https://doi.org/10.1038/nrgastro.2015.186.CrossRefPubMed

Park JH, Peyrin-Biroulet L, Eisenhut M, Shin JI. IBD immunopathogenesis: a comprehensive review of inflammatory molecules. Autoimmun Rev. 2017;16:416–26. https://doi.org/10.1016/j.autrev.2017.02.013.CrossRefPubMed

Lai LJ, Shen J, Ran ZH. Natural killer T cells and ulcerative colitis. Cell Immunol. 2019;335:1–5. https://doi.org/10.1016/j.cellimm.2018.08.010.CrossRefPubMed

Lockhart A, Mucida D, Parsa R. Immunity to enteric viruses. Immunity. 2022;55:800–18. https://doi.org/10.1016/j.immuni.2022.04.007.CrossRefPubMedCentralPubMed

Pandolfini L, Barbieri I, Bannister AJ, Hendrick A, Andrews B, Webster N, Murat P, Mach P, Brandi R, Robson SC, Migliori V, Alendar A, d’Onofrio M, Balasubramanian S, Kouzarides T. METTL1 promotes let-7 MicroRNA processing via m7G methylation. Mol Cell. 2019;74:1278-1290.e9. https://doi.org/10.1016/j.molcel.2019.03.040.CrossRefPubMedCentralPubMed

Luo Y, Yao Y, Wu P, Zi X, Sun N, He J. The potential role of N7-methylguanosine (m7G) in cancer. J Hematol Oncol. 2022;15:63. https://doi.org/10.1186/s13045-022-01285-5.CrossRefPubMedCentralPubMed

10.

Yang S, Zhou J, Chen Z, Sun Q, Zhang D, Feng Y, Wang X, Sun Y. A novel m7G-related lncRNA risk model for predicting prognosis and evaluating the tumor immune microenvironment in colon carcinoma. Front Oncol. 2022;12: 934928. https://doi.org/10.3389/fonc.2022.934928.CrossRefPubMedCentralPubMed

11.

Li X-Y, Wang S-L, Chen D-H, Liu H, You J-X, Su L-X, Yang X-T. Construction and validation of a m7G-related gene-based prognostic model for gastric cancer. Front Oncol. 2022;12: 861412. https://doi.org/10.3389/fonc.2022.861412.CrossRefPubMedCentralPubMed

12.

Cai X, Shi W, Lian J, Zhang G, Cai Y, Zhu L. Characterization of immune landscape and development of a novel N7-methylguanine-related gene signature to aid therapy in recurrent aphthous stomatitis. Inflamm Res. 2023;72:133–48. https://doi.org/10.1007/s00011-022-01665-0.CrossRefPubMed

13.

Dong K, Gu D, Shi J, Bao Y, Fu Z, Fang Y, Qu L, Zhu W, Jiang A, Wang L. Identification and verification of m7G modification patterns and characterization of tumor microenvironment infiltration via multi-omics analysis in clear cell renal cell carcinoma. Front Immunol. 2022;13: 874792. https://doi.org/10.3389/fimmu.2022.874792.CrossRefPubMedCentralPubMed

14.

Zhao Z, Qing Y, Dong L, Han L, Wu D, Li Y, Li W, Xue J, Zhou K, Sun M, Tan B, Chen Z, Shen C, Gao L, Small A, Wang K, Leung K, Zhang Z, Qin X, Deng X, Xia Q, Su R, Chen J. QKI shuttles internal m7G-modified transcripts into stress granules and modulates mRNA metabolism. Cell. 2023;S0092–8674(23):00598–606. https://doi.org/10.1016/j.cell.2023.05.047.CrossRef

15.

Comprehensive analysis of cuproptosis-related genes in immune infiltration and diagnosis in ulcerative colitis—PubMed, (n.d.). https://pubmed.ncbi.nlm.nih.gov/36389705/ (Accessed 14 July 2023).

16.

Kim Y, Kang JW, Kang J, Kwon EJ, Ha M, Kim YK, Lee H, Rhee J-K, Kim YH. Novel deep learning-based survival prediction for oral cancer by analyzing tumor-infiltrating lymphocyte profiles through CIBERSORT. Oncoimmunology. 2021;10:1904573. https://doi.org/10.1080/2162402X.2021.1904573.CrossRefPubMedCentralPubMed

17.

Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16:284–7. https://doi.org/10.1089/omi.2011.0118.CrossRefPubMedCentralPubMed

18.

Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9:559. https://doi.org/10.1186/1471-2105-9-559.CrossRefPubMedCentralPubMed

19.

Langfelder P, Luo R, Oldham MC, Horvath S. Is my network module preserved and reproducible? PLoS Comput Biol. 2011;7: e1001057. https://doi.org/10.1371/journal.pcbi.1001057.CrossRefPubMedCentralPubMed

20.

Zuo T, Lu X-J, Zhang Y, Cheung CP, Lam S, Zhang F, Tang W, Ching JYL, Zhao R, Chan PKS, Sung JJY, Yu J, Chan FKL, Cao Q, Sheng J-Q, Ng SC. Gut mucosal virome alterations in ulcerative colitis. Gut. 2019;68:1169–79. https://doi.org/10.1136/gutjnl-2018-318131.CrossRefPubMed

21.

Xia X, Wang Y, Zheng JC. Internal m7G methylation: a novel epitranscriptomic contributor in brain development and diseases. Mol Ther Nucleic Acids. 2023;31:295–308. https://doi.org/10.1016/j.omtn.2023.01.003.CrossRefPubMedCentralPubMed

22.

Emerging roles of RNA methylation in gastrointestinal cancers - PubMed, (n.d.). https://pubmed.ncbi.nlm.nih.gov/33372610/ (Accessed 14 July 2023).

23.

Montañés-Agudo P, Aufiero S, Schepers EN, van der Made I, Cócera-Ortega L, Ernault AC, Richard S, Kuster DWD, Christoffels VM, Pinto YM, Creemers EE. The RNA-binding protein QKI governs a muscle-specific alternative splicing program that shapes the contractile function of cardiomyocytes. Cardiovasc Res. 2023;119:1161–74. https://doi.org/10.1093/cvr/cvad007.CrossRefPubMedCentralPubMed

24.

Tian Y, Xu J, Li Y, Zhao R, Du S, Lv C, Wu W, Liu R, Sheng X, Song Y, Bi X, Li G, Li M, Wu X, Lou P, You H, Cui W, Sun J, Shuai J, Ren F, Zhang B, Guo M, Hou X, Wu K, Xue L, Zhang H, Plikus MV, Cong Y, Lengner CJ, Liu Z, Yu Z. MicroRNA-31 reduces inflammatory signaling and promotes regeneration in colon epithelium, and delivery of mimics in microspheres reduces colitis in mice. Gastroenterology. 2019;156:2281-2296.e6. https://doi.org/10.1053/j.gastro.2019.02.023.CrossRefPubMed

25.

Xie Z, Wang Y, Yang G, Han J, Zhu L, Li L, Zhang S. The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease. Cell Death Dis. 2021;12:79. https://doi.org/10.1038/s41419-021-03395-3.CrossRefPubMedCentralPubMed

26.

Neumann DP, Goodall GJ, Gregory PA. The quaking RNA-binding proteins as regulators of cell differentiation. Wiley Interdiscip Rev RNA. 2022;13: e1724. https://doi.org/10.1002/wrna.1724.CrossRefPubMedCentralPubMed

27.

Yang L, Wu G, Wu Q, Peng L, Yuan L. METTL3 overexpression aggravates LPS-induced cellular inflammation in mouse intestinal epithelial cells and DSS-induced IBD in mice. Cell Death Discov. 2022;8:62. https://doi.org/10.1038/s41420-022-00849-1.CrossRefPubMedCentralPubMed

28.

Wang L, Zhai D-S, Ruan B-J, Xu C-M, Ye Z-C, Lu H-Y, Jiang Y-H, Wang Z-Y, Xiang A, Yang Y, Yuan J-L, Lu Z-F. Quaking deficiency amplifies inflammation in experimental endotoxemia via the aryl hydrocarbon receptor/signal transducer and activator of transcription 1-NF-κB pathway. Front Immunol. 2017;8:1754. https://doi.org/10.3389/fimmu.2017.01754.CrossRefPubMedCentralPubMed

29.

Roffey J, Rosse C, Linch M, Hibbert A, McDonald NQ, Parker PJ. Protein kinase C intervention: the state of play. Curr Opin Cell Biol. 2009;21:268–79. https://doi.org/10.1016/j.ceb.2009.01.019.CrossRefPubMed

30.

Patergnani S, Marchi S, Rimessi A, Bonora M, Giorgi C, Mehta KD, Pinton P. PRKCB/protein kinase C, beta and the mitochondrial axis as key regulators of autophagy. Autophagy. 2013;9:1367–85. https://doi.org/10.4161/auto.25239.CrossRefPubMed

31.

Deretic V. Autophagy in inflammation, infection, and immunometabolism. Immunity. 2021;54:437–53. https://doi.org/10.1016/j.immuni.2021.01.018.CrossRefPubMedCentralPubMed

32.

Foerster EG, Mukherjee T, Cabral-Fernandes L, Rocha JDB, Girardin SE, Philpott DJ. How autophagy controls the intestinal epithelial barrier. Autophagy. 2022;18:86–103. https://doi.org/10.1080/15548627.2021.1909406.CrossRefPubMed

33.

Song J, Baek I-J, Chun C-H, Jin E-J. Dysregulation of the NUDT7-PGAM1 axis is responsible for chondrocyte death during osteoarthritis pathogenesis. Nat Commun. 2018;9:3427. https://doi.org/10.1038/s41467-018-05787-0.CrossRefPubMedCentralPubMed

34.

Wu H, Li L, Chen K-M, Homolka D, Gos P, Fleury-Olela F, McCarthy AA, Pillai RS. Decapping enzyme NUDT12 partners with BLMH for cytoplasmic surveillance of NAD-capped RNAs. Cell Rep. 2019;29:4422-4434.e13. https://doi.org/10.1016/j.celrep.2019.11.108.CrossRefPubMed

35.

Song M-G, Bail S, Kiledjian M. Multiple Nudix family proteins possess mRNA decapping activity. RNA. 2013;19:390–9. https://doi.org/10.1261/rna.037309.112.CrossRefPubMedCentralPubMed

36.

Fan S, Liang Z, Gao Z, Pan Z, Han S, Liu X, Zhao C, Yang W, Pan Z, Feng W. Identification of the key genes and pathways in prostate cancer. Oncol Lett. 2018;16:6663–9. https://doi.org/10.3892/ol.2018.9491.CrossRefPubMedCentralPubMed

37.

Costales-Carrera A, Fernández-Barral A, Bustamante-Madrid P, Domínguez O, Guerra-Pastrián L, Cantero R, Del Peso L, Burgos A, Barbáchano A, Muñoz A. Comparative study of organoids from patient-derived normal and tumor colon and rectal tissue. Cancers (Basel). 2020;12:2302. https://doi.org/10.3390/cancers12082302.CrossRefPubMed

38.

Hupé M, Rivière P, Nancey S, Roblin X, Altwegg R, Filippi J, Fumery M, Bouguen G, Peyrin-Biroulet L, Bourreille A, Caillo L, Simon M, Goutorbe F, Laharie D. Comparative efficacy and safety of vedolizumab and infliximab in ulcerative colitis after failure of a first subcutaneous anti-TNF agent: a multicentre cohort study. Aliment Pharmacol Ther. 2020;51:852–60. https://doi.org/10.1111/apt.15680.CrossRefPubMed

39.

Favale A, Onali S, Caprioli F, Pugliese D, Armuzzi A, Macaluso FS, Orlando A, Viola A, Fries W, Rispo A, Castiglione F, Mocci G, Chicco F, Usai P, Calabrese E, Biancone L, Monteleone G, Fantini MC. Italian group for the study of inflammatory bowel disease (IG-IBD), comparative efficacy of vedolizumab and adalimumab in ulcerative colitis patients previously treated with infliximab. Inflamm Bowel Dis. 2019;25:1805–12. https://doi.org/10.1093/ibd/izz057.CrossRefPubMed

Titel: Identification of novel N7-methylguanine-related gene signatures associated with ulcerative colitis and the association with biological therapy
verfasst von: Lichao Yang
Lianwen Yuan
Publikationsdatum: 27.10.2023
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 12/2023
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-023-01806-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Auf Antibiotika verzichten? Was bei unkomplizierter Zystitis hilft

15.05.2024 Harnwegsinfektionen Nachrichten

Welche Antibiotika darf man bei unkomplizierter Zystitis verwenden und wovon sollte man die Finger lassen? Welche pflanzlichen Präparate können helfen? Was taugt der zugelassene Impfstoff? Antworten vom Koordinator der frisch überarbeiteten S3-Leitlinie, Prof. Florian Wagenlehner.

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Intervallfasten zur Regeneration des Herzmuskels?

14.05.2024 Herzinfarkt Nachrichten

Die Nahrungsaufnahme auf wenige Stunden am Tag zu beschränken, hat möglicherweise einen günstigen Einfluss auf die Prognose nach akutem ST-Hebungsinfarkt. Darauf deutet eine Studie an der Uniklinik in Halle an der Saale hin.

Klimaschutz beginnt bei der Wahl des Inhalators

14.05.2024 Klimawandel Podcast

Auch kleine Entscheidungen im Alltag einer Praxis können einen großen Beitrag zum Klimaschutz leisten. Die neue Leitlinie zur "klimabewussten Verordnung von Inhalativa" geht mit gutem Beispiel voran, denn der Wechsel vom klimaschädlichen Dosieraerosol zum Pulverinhalator spart viele Tonnen CO₂. Leitlinienautor PD Dr. Guido Schmiemann erklärt, warum nicht nur die Umwelt, sondern auch Patientinnen und Patienten davon profitieren.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Objective

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2023

Treg plasticity and human diseases

Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation

Mitochondrial dysfunction: a new molecular mechanism of intervertebral disc degeneration

Application of omics in Sjögren’s syndrome

Lidocaine pretreatment attenuates inflammatory response and protects against sepsis-induced acute lung injury via inhibiting potassium efflux-dependent NLRP3 activation

STAT6 promoting oxalate crystal deposition-induced renal fibrosis by mediating macrophage-to-myofibroblast transition via inhibiting fatty acid oxidation