{"title":"The m6A reader IGF2BP3 promotes HCC progression by enhancing MCM10 stability.","authors":"Lianwu Zhao, Hongyan Huang, Linfei Luo, Zixiang Huang, Zhengqiang Wu, Fenfen Wang, Zhili Wen","doi":"10.1038/s41598-025-93062-w","DOIUrl":null,"url":null,"abstract":"<p><p>Abnormal N6-methyladenosine (m6A) modifications were associated with the occurrence, development, and metastasis of cancer. However, the functions and mechanisms of m6A regulators in cancer remained largely elusive and should be explored. Here, we identified that insulin like growth Factor 2 mRNA binding protein 3 (IGF2BP3) was specifically overexpressed and associated with poor prognosis in liver hepatocellular carcinoma (HCC). Importantly, IGF2BP3 promoted HCC cells progression in an m6A-dependent manner, IGF2BP3 silencing significantly inhibited proliferation and migratory ability of tumor cells in vitro and in in vivo. Mechanistically, IGF2BP3 interacted with minichromosomal maintenance complex component (MCM10) mRNAs to prolong stability of m6A-modified RNA. Therefore, our findings indicated that m6A reader IGF2BP3 contributed to tumorigenesis and poor prognosis, providing a potential prognostic biomarker and therapeutic target for HCC.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"8204"},"PeriodicalIF":3.9000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894129/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-93062-w","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Abnormal N6-methyladenosine (m6A) modifications were associated with the occurrence, development, and metastasis of cancer. However, the functions and mechanisms of m6A regulators in cancer remained largely elusive and should be explored. Here, we identified that insulin like growth Factor 2 mRNA binding protein 3 (IGF2BP3) was specifically overexpressed and associated with poor prognosis in liver hepatocellular carcinoma (HCC). Importantly, IGF2BP3 promoted HCC cells progression in an m6A-dependent manner, IGF2BP3 silencing significantly inhibited proliferation and migratory ability of tumor cells in vitro and in in vivo. Mechanistically, IGF2BP3 interacted with minichromosomal maintenance complex component (MCM10) mRNAs to prolong stability of m6A-modified RNA. Therefore, our findings indicated that m6A reader IGF2BP3 contributed to tumorigenesis and poor prognosis, providing a potential prognostic biomarker and therapeutic target for HCC.
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