{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:17:01Z","timestamp":1787026621265,"version":"build-2736575974"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203251, 82173299, 81872209, 81870602"],"award-info":[{"award-number":["82203251, 82173299, 81872209, 81870602"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with endemic prevalence in southern China. Emerging evidence highlights the critical function of the N6-methyladenosine (m\n                      <jats:sup>6<\/jats:sup>\n                      A) methylation in NPC progression, where sustained cytokine activity contributes to immunosuppression and immune evasion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing datasets were obtained from the GEO database. High-dimensional downstream analyses, including hdWGCNA, cell\u2013cell communication, and pseudotime analysis was performed to characterize cellular interactions and transcriptional programs. Machine learning algorithms and immune infiltration profiling were integrated with MeRIP-seq to identify the key m\n                      <jats:sup>6<\/jats:sup>\n                      A-regulated gene. The post-transcriptional regulatory role was further validated in NPC cells with overexpression or knockdown of METTL14, or in cells with YWHAH silenced.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      B cells were identified as the primary senders to the TNF pathway, with epithelial and myeloid cells acting as influencers and receivers. YWHAH emerged as a key TNF-associated, m\n                      <jats:sup>6<\/jats:sup>\n                      A-regulated gene, with elevated expression in naive\/GC B cells, interleukin (IL)-1\u03b2+ tumor-associated macrophages, and differentiated epithelial cells. METTL14-deficient increased YWHAH transcript abundance and RNA stability, whereas TNF-\u03b1 stimulation further enhanced YWHAH expression. Conversely, YWHAH knockdown impaired NPC cell migration and upregulated IL\u22126\/IL\u22128 expression, effects that were partially rescued by TNF\u2212\u03b1 treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Integration of multi-omics data facilitated the identification of YWHAH as a METTL14-regulated gene, which plays a pivotal role in the NPC immune microenvironment. The elevated expression of YWHAH indicates its role in regulating immune balance. Together these findings suggest a potential regulatory link between TNF-\u03b1, YWHAH and METTL14 in the context of NPC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1717039","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:31:33Z","timestamp":1770013893000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["METTL14 modulates the nasopharyngeal carcinoma microenvironment via m6A-modified YWHAH identified through single-cell and machine learning analyses"],"prefix":"10.3389","volume":"17","author":[{"given":"Zuming","family":"Liang","sequence":"first","affiliation":[{"name":"Laboratory Animal Management Center, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University","place":["Guangzhou, China"]},{"name":"Division of Life Science, State Key Laboratory for Nervous System Disorders, The Hong Kong University of Science and 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