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However, the function of m\n                    <jats:sup>6<\/jats:sup>\n                    A reader proteins in HCC remains poorly understood. Here, we elucidate the role and mechanism of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in HCC. In here, we analyzed IGF2BP2 expression in HCC using bioinformatics and clinical samples. The functional role of the IGF2BP2-RELB regulatory axis in HCC progression was assessed through cytological assays and a xenograft HCC mouse model. RNA sequencing, Western blotting, Actinomycin-D assays, and RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP) assays were performed to investigate the regulatory mechanisms of IGF2BP2 on RELB expression. We found high expression of IGF2BP2 in HCC was positively correlated with poor prognosis. Gain- and loss-of-function assays demonstrated that IGF2BP2 was essential for HCC cell proliferation and migration. IGF2BP2 directly bound to RELB mRNA and enhanced its stability via the KH3\/4 domain. Upregulated RELB promoted nuclear translocation of the RELB:p52\u00a0dimer, leading to activation of the NF-\u03baB signaling pathway. Furthermore, inhibition of IGF2BP2 and RELB suppressed HCC tumor progression both\u00a0in vitro\u00a0and\u00a0in vivo. Our study demonstrates that IGF2BP2 plays a critical role in HCC progression by stabilizing RELB mRNA and activating the NF-\u03baB signaling pathway. The results suggest that IGF2BP2 may be a potential therapeutic strategy for HCC.\n                  <\/jats:p>","DOI":"10.1186\/s43556-026-00465-w","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:43:52Z","timestamp":1778154232000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The m6A reader IGF2BP2 promotes hepatocellular carcinoma progression via enhancing RELB stability"],"prefix":"10.1186","volume":"7","author":[{"given":"Hehua","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuyi","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanxun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3756-198X","authenticated-orcid":false,"given":"Wei","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"issue":"3","key":"465_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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For HCC patient specimens, the approval was granted by the Institutional Ethics Committee of Nanjing Drum Tower Hospital (No. 2024\u2013356-03). The animal experiments were approved by the Ethics Committee of Nanjing First Hospital and carried out under the guidance of the Animal Experiment Center of Nanjing First Hospital (No. DWSY-24089545).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"62"}}