{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:39:22Z","timestamp":1767595162799,"version":"3.48.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The E3 ubiquitin ligase Pellino1 (PELI1) is ubiquitously expressed in human tissues and primarily modulates inflammatory and immune responses; however, its pan-cancer biological significance remains poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed a combination of R software and online bioinformatics platforms\u2014including UALCAN, HPA, GEPIA2, cBioPortal, STRING, TISIDB, SRAMP, LinkedOmics, and Sangerbox\u2014to systematically characterize PELI1 in human tumors. Our analyses encompassed its abnormal expression, genetic alterations, prognostic and diagnostic relevance, and epigenetic regulation. Focusing on liver hepatocellular carcinoma (LIHC), we further explored the oncogenic functions of PELI1, its associated signaling pathways, and immunomodulatory roles. Key bioinformatic predictions were subsequently validated through\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments using LIHC cell lines, including functional assays (proliferation, apoptosis, and cell cycle) and signaling pathway analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PELI1 was frequently overexpressed across multiple tumor types and mainly correlated with poor patient prognosis. The highest frequency of PELI1 alterations was observed in patients with diffuse large B-cell lymphoma, primarily in the form of copy number amplification, while R145Q\/W represented the most recurrent mutation sites. PELI1 may drives cancer progression through epigenetic regulation involving DNA methylation and N6-methyladenosine (m6A) RNA modifications. PELI1 could potentially serve as a novel biomarker for diagnosing different cancer types. In LIHC specifically, PELI1 expression was significantly elevated compared to adjacent non-tumor tissues. Functional studies revealed that PELI1 modulated cell apoptosis, cell cycle progression, immune responses and the MAPK-ERK pathway in LIHC. Furthermore, PELI1 may regulate immune checkpoints to influence the immune responses. PELI1 expression was positively correlated with the IC50 of hepatocellular carcinoma investigational drug\u2013CFI-402257. Experimental knockdown of PELI1 in LIHC cell lines suppressed proliferation, promoted apoptosis and induced G1-phase cell cycle arrest via MAPK-ERK pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This pan-cancer study revealed the diagnostic, prognostic and immunomodulatory potential, along with the biological function and mechanism of PELI1, supporting its role as a promising therapeutic target in LIHC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1682086","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T06:36:19Z","timestamp":1767594979000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PELI1 in human cancers: a pan-cancer exploration of its molecular function, clinical significance, and immunomodulatory roles"],"prefix":"10.3389","volume":"16","author":[{"given":"Yan","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiale","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoran","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA: Cancer J For Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.26355\/eurrev_201806_15270","article-title":"Tumor microenvironment: recent advances in various cancer treatments","volume":"22","author":"Wang","year":"2018","journal-title":"Eur Rev For Med Pharmacol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nature25795","article-title":"Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours","volume":"555","author":"Ma","year":"2018","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1361657","article-title":"Scinderin is a potential prognostic biomarker and correlated with immunological regulation: from pan-cancer analysis to liver hepatocellular carcinoma","volume":"15","author":"Zhai","year":"2024","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.007","article-title":"Ubiquitin makes its mark on immune regulation","volume":"33","author":"Malynn","year":"2010","journal-title":"Immunity"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1292022","article-title":"Biology of Pellino1: a potential therapeutic target for inflammation in diseases and cancers","volume":"14","author":"Yan","year":"2023","journal-title":"Front In Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2017.05.002","article-title":"UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses","volume":"19","author":"Chandrashekar","year":"2017","journal-title":"Neoplasia (New York N.Y.)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. 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