1887

Abstract

The aetiological mechanisms of in laryngeal cancer remain unclear. This study aimed to reveal the epigenetic signature induced by in laryngeal squamous cell carcinoma (LSCC). Combined analysis of methylome and transcriptome data was performed to address the functional role of in laryngeal cancer. Twenty-nine differentially expressed methylation-driven genes were identified by mapping the methylation levels of significant differential methylation sites to the expression levels of related genes. The combined analysis revealed that promoted Janus kinase 3 (JAK3) gene expression in LSCC. Further validation found decreased methylation and elevated expression of JAK3 in the treated LSCC cell group; abundance and JAK3 gene expression had a positive correlation in tumour tissues. This analysis provides a novel understanding of the impact of in the methylome and transcriptome of laryngeal cancer. Identification of these epigenetic regulatory mechanisms opens up new avenues for mechanistic studies to explore novel therapeutic strategies.

Funding
This study was supported by the:
  • Shanghai Sailing Program (Award 22YF1405700)
    • Principle Award Recipient: Chi-YaoHsueh
  • National Natural Science Foundation of China (Award 81972529)
    • Principle Award Recipient: HongliGong
  • National Natural Science Foundation of China (Award 81502343)
    • Principle Award Recipient: LiangZhou
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.001221
2024-03-27
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/mgen/10/3/mgen001221.html?itemId=/content/journal/mgen/10.1099/mgen.0.001221&mimeType=html&fmt=ahah

References

  1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71:209–249 [View Article] [PubMed]
    [Google Scholar]
  2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021; 71:7–33 [View Article] [PubMed]
    [Google Scholar]
  3. Steuer CE, El-Deiry M, Parks JR, Higgins KA, Saba NF. An update on larynx cancer. CA Cancer J Clin 2017; 67:31–50 [View Article] [PubMed]
    [Google Scholar]
  4. Wang N, Fang J-Y. Fusobacterium nucleatum, a key pathogenic factor and microbial biomarker for colorectal cancer. Trends Microbiol 2022; 31:159–172 [View Article] [PubMed]
    [Google Scholar]
  5. Li Z, Shi C, Zheng J, Guo Y, Fan T et al. Fusobacterium nucleatum predicts a high risk of metastasis for esophageal squamous cell carcinoma. BMC Microbiol 2021; 21:301 [View Article]
    [Google Scholar]
  6. Chen Z, Wong PY, Ng CWK, Lan L, Fung S et al. The intersection between oral microbiota, host gene methylation and patient outcomes in head and neck squamous cell carcinoma. Cancers 2020; 12:3425 [View Article] [PubMed]
    [Google Scholar]
  7. Zhang Y, Zhang L, Zheng S, Li M, Xu C et al. Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis. Gut Microbes 2022; 14:2038852 [View Article] [PubMed]
    [Google Scholar]
  8. Xu C, Fan L, Lin Y, Shen W, Qi Y et al. Fusobacterium nucleatum promotes colorectal cancer metastasis through miR-1322/CCL20 axis and M2 polarization. Gut Microbes 2021; 13:1980347 [View Article] [PubMed]
    [Google Scholar]
  9. Gong H, Shi Y, Xiao X, Cao P, Wu C et al. Alterations of microbiota structure in the larynx relevant to laryngeal carcinoma. Sci Rep 2017; 7:5507 [View Article] [PubMed]
    [Google Scholar]
  10. Bernstein BE, Meissner A, Lander ES. The mammalian epigenome. Cell 2007; 128:669–681 [View Article] [PubMed]
    [Google Scholar]
  11. Ferry L, Fournier A, Tsusaka T, Adelmant G, Shimazu T et al. Methylation of DNA ligase 1 by G9a/GLP recruits UHRF1 to replicating DNA and regulates DNA methylation. Mol Cell 2017; 67:550–565 [View Article] [PubMed]
    [Google Scholar]
  12. Zheng X, Zhang N, Wu H-J, Wu H. Estimating and accounting for tumor purity in the analysis of DNA methylation data from cancer studies. Genome Biol 2017; 18:17 [View Article] [PubMed]
    [Google Scholar]
  13. Romano KA, Martinez-Del Campo A, Kasahara K, Chittim CL, Vivas EI et al. Metabolic, epigenetic, and transgenerational effects of gut bacterial choline consumption. Cell Host Microbe 2017; 22:279–290 [View Article] [PubMed]
    [Google Scholar]
  14. Chen S, Zhang L, Li M, Zhang Y, Sun M et al. Fusobacterium nucleatum reduces METTL3-mediated m6A modification and contributes to colorectal cancer metastasis. Nat Commun 2022; 13:1248 [View Article] [PubMed]
    [Google Scholar]
  15. Kim SY, Chu KC, Lee HR, Lee KS, Carey TE. Establishment and characterization of nine new head and neck cancer cell lines. Acta Otolaryngol 1997; 117:775–784 [View Article] [PubMed]
    [Google Scholar]
  16. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H et al. Gene ontology: tool for the unification of biology. Nat Genet 2000; 25:25–29 [View Article]
    [Google Scholar]
  17. Kanehisa M, Goto S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000; 28:27–30 [View Article] [PubMed]
    [Google Scholar]
  18. Bullman S, Pedamallu CS, Sicinska E, Clancy TE, Zhang X et al. Analysis of Fusobacterium persistence and antibiotic response in colorectal cancer. Science 2017; 358:1443–1448 [View Article] [PubMed]
    [Google Scholar]
  19. Hsueh C-Y, Lau H-C, Huang Q, Gong H, Sun J et al. Fusobacterium nucleatum impairs DNA mismatch repair and stability in patients with squamous cell carcinoma of the head and neck. Cancer 2022; 128:3170–3184 [View Article] [PubMed]
    [Google Scholar]
  20. Zhang S, Li C, Liu J, Geng F, Shi X et al. Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway. FEBS J 2020; 287:4032–4047 [View Article] [PubMed]
    [Google Scholar]
  21. Larue L, Bellacosa A. Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3’ kinase/AKT pathways. Oncogene 2005; 24:7443–7454 [View Article] [PubMed]
    [Google Scholar]
  22. Long X, Wong CC, Tong L, Chu ESH, Ho Szeto C et al. Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity. Nat Microbiol 2019; 4:2319–2330 [View Article] [PubMed]
    [Google Scholar]
  23. Liu C, Feng X, Wang B, Wang X, Wang C et al. Bone marrow mesenchymal stem cells promote head and neck cancer progression through periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin. Cancer Sci 2018; 109:688–698 [View Article] [PubMed]
    [Google Scholar]
  24. Fei Z, Deng Z, Zhou L, Li K, Xia X et al. PD-L1 induces epithelial-mesenchymal transition in nasopharyngeal carcinoma cells through activation of the PI3K/AKT pathway. Oncol Res 2019; 27:801–807 [View Article] [PubMed]
    [Google Scholar]
  25. Wang X, Chen Q. FERMT1 knockdown inhibits oral squamous cell carcinoma cell epithelial-mesenchymal transition by inactivating the PI3K/AKT signaling pathway. BMC Oral Health 2021; 21:598 [View Article] [PubMed]
    [Google Scholar]
  26. Hsueh C-Y, Huang Q, Gong H, Shen Y, Sun J et al. A positive feed-forward loop between Fusobacterium nucleatum and ethanol metabolism reprogramming drives laryngeal cancer progression and metastasis. iScience 2022; 25:103829 [View Article] [PubMed]
    [Google Scholar]
  27. Lai SY, Childs EE, Xi S, Coppelli FM, Gooding WE et al. Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma. Oncogene 2005; 24:4442–4449 [View Article] [PubMed]
    [Google Scholar]
  28. Su S-C, Yeh C-M, Lin C-W, Hsieh Y-H, Chuang C-Y et al. A novel melatonin-regulated lncRNA suppresses TPA-induced oral cancer cell motility through replenishing PRUNE2 expression. J Pineal Res 2021; 71:e12760 [View Article] [PubMed]
    [Google Scholar]
  29. Zhang Y-G, Lu R, Wu S, Chatterjee I, Zhou D et al. Vitamin D receptor protects against dysbiosis and tumorigenesis via the JAK/STAT pathway in intestine. Cell Mol Gastroenterol Hepatol 2020; 10:729–746 [View Article] [PubMed]
    [Google Scholar]
  30. Xia X, Wu WKK, Wong SH, Liu D, Kwong TNY et al. Bacteria pathogens drive host colonic epithelial cell promoter hypermethylation of tumor suppressor genes in colorectal cancer. Microbiome 2020; 8:108 [View Article] [PubMed]
    [Google Scholar]
  31. Gutierrez-Arcelus M, Lappalainen T, Montgomery SB, Buil A, Ongen H et al. Passive and active DNA methylation and the interplay with genetic variation in gene regulation. Elife 2013; 2:e00523 [View Article] [PubMed]
    [Google Scholar]
  32. Orozco LD, Morselli M, Rubbi L, Guo W, Go J et al. Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice. Cell Metab 2015; 21:905–917 [View Article] [PubMed]
    [Google Scholar]
  33. Weinberg DN, Papillon-Cavanagh S, Chen H, Yue Y, Chen X et al. The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape. Nature 2019; 573:281–286 [View Article] [PubMed]
    [Google Scholar]
  34. Dang J, Bian Y-Q, Sun JY, Chen F, Dong G-Y et al. MicroRNA-137 promoter methylation in oral lichen planus and oral squamous cell carcinoma. J Oral Pathol Med 2013; 42:315–321 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.001221
Loading
/content/journal/mgen/10.1099/mgen.0.001221
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error