{"title":"ALKBH1-mediated N6-methyladenosine methylation of TRAF1 promotes osteosarcoma proliferation and metastasis.","authors":"Zhichao Wang, Yuli Fang, Yang Yu, Haile Pan","doi":"10.62347/ALXR1853","DOIUrl":null,"url":null,"abstract":"<p><p>Osteosarcoma (OS) is a highly malignant bone tumor with poor prognosis and limited therapeutic options. Recent studies have highlighted the critical role of RNA modifications, particularly N6-methyladenosine (m6A) methylation, in cancer progression. This study aimed to investigate the role of ALKBH1, a m6A demethylase, in the proliferation and metastasis of OS through the regulation of TRAF1. Our findings showed that lower ALKBH1 expression correlates with poorer overall survival in OS patients. Knockdown of ALKBH1 significantly enhanced the proliferation, migration, and clonogenicity of OS cell lines (MG63 and HOS cells), while overexpression had the opposite effects. Transcriptomic analysis revealed that ALKBH1 regulates the expression of key oncogenes, including TRAF1, through m6A methylation. m6A-RIP and qPCR assays further confirmed that overexpression of ALKBH1 significantly decreased the m6A methylation and expression of TRAF1 in both MG63 and HOS cells, and ALKBH1 knockdown had the opposite roles. Combined knockdown of ALKBH1 and TRAF1 further reduced the oncogenic properties of osteosarcoma cells compared to individual knockdown for ALKBH1. In conclusion, ALKBH1 silence promotes osteosarcoma proliferation and metastasis by regulating TRAF1 expression through m6A methylation. Targeting the ALKBH1-TRAF1 axis may provide a novel therapeutic strategy for osteosarcoma.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 1","pages":"375-389"},"PeriodicalIF":3.6000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815365/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.62347/ALXR1853","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
ALKBH1-mediated N6-methyladenosine methylation of TRAF1 promotes osteosarcoma proliferation and metastasis.
Osteosarcoma (OS) is a highly malignant bone tumor with poor prognosis and limited therapeutic options. Recent studies have highlighted the critical role of RNA modifications, particularly N6-methyladenosine (m6A) methylation, in cancer progression. This study aimed to investigate the role of ALKBH1, a m6A demethylase, in the proliferation and metastasis of OS through the regulation of TRAF1. Our findings showed that lower ALKBH1 expression correlates with poorer overall survival in OS patients. Knockdown of ALKBH1 significantly enhanced the proliferation, migration, and clonogenicity of OS cell lines (MG63 and HOS cells), while overexpression had the opposite effects. Transcriptomic analysis revealed that ALKBH1 regulates the expression of key oncogenes, including TRAF1, through m6A methylation. m6A-RIP and qPCR assays further confirmed that overexpression of ALKBH1 significantly decreased the m6A methylation and expression of TRAF1 in both MG63 and HOS cells, and ALKBH1 knockdown had the opposite roles. Combined knockdown of ALKBH1 and TRAF1 further reduced the oncogenic properties of osteosarcoma cells compared to individual knockdown for ALKBH1. In conclusion, ALKBH1 silence promotes osteosarcoma proliferation and metastasis by regulating TRAF1 expression through m6A methylation. Targeting the ALKBH1-TRAF1 axis may provide a novel therapeutic strategy for osteosarcoma.
期刊介绍：
The American Journal of Cancer Research (AJCR) (ISSN 2156-6976), is an independent open access, online only journal to facilitate rapid dissemination of novel discoveries in basic science and treatment of cancer. It was founded by a group of scientists for cancer research and clinical academic oncologists from around the world, who are devoted to the promotion and advancement of our understanding of the cancer and its treatment. The scope of AJCR is intended to encompass that of multi-disciplinary researchers from any scientific discipline where the primary focus of the research is to increase and integrate knowledge about etiology and molecular mechanisms of carcinogenesis with the ultimate aim of advancing the cure and prevention of this increasingly devastating disease. To achieve these aims AJCR will publish review articles, original articles and new techniques in cancer research and therapy. It will also publish hypothesis, case reports and letter to the editor. Unlike most other open access online journals, AJCR will keep most of the traditional features of paper print that we are all familiar with, such as continuous volume, issue numbers, as well as continuous page numbers to retain our comfortable familiarity towards an academic journal.
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