{"title":"METTL11A通过调控p38-MAPK通路作为急性髓系白血病的新治疗靶点。","authors":"Ju Li, Jiasi Zhang, Pei Zhang","doi":"10.21037/tcr-2025-602","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) represents a heterogeneous blood malignancy and is the most common and severe acute leukemia in adult. The METTL gene family is increasingly being recognized as involved in cancer progression. The aim of the study is to elaborate on the specific role of METTL11A in AML.</p><p><strong>Methods: </strong>In this research, cell viability, transwell assay, and scratch wound assay were utilized to assess cell proliferation and migration in AML cells. Western blot was used to determine the expression of proteins and the activation of signal pathway. Virtual screening was performed to obtain potential inhibitors of METTL11A.</p><p><strong>Results: </strong>Our findings indicated that METTL11A expression levels were strongly associated with AML patients' prognosis. Overexpressed METTL11A by constructing stable cell lines promoted proliferation and migration in AML cells. Conversely, knockdown of METTL11A inhibited cell viability and migration. Through gene sets enrichment analysis, we validated the inactivated p38-mitogen-activated protein kinase (MAPK) pathway under silenced METTL11A expression. In high throughput molecular docking, S-Adenosyl-L-methionine disulfate tosylate was predicted to bind METTL11A, which was validated to inhibit cell proliferation and migration.</p><p><strong>Conclusions: </strong>The results suggested that METTL11A is a novel biomarker and therapeutic target in AML, which is mediated by suppressed MAPK pathway.</p>","PeriodicalId":23216,"journal":{"name":"Translational cancer research","volume":"14 8","pages":"4561-4573"},"PeriodicalIF":1.7000,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432591/pdf/","citationCount":"0","resultStr":"{\"title\":\"METTL11A serves as a novel therapeutic target for acute myeloid leukemia through regulation of the p38-MAPK pathway.\",\"authors\":\"Ju Li, Jiasi Zhang, Pei Zhang\",\"doi\":\"10.21037/tcr-2025-602\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Acute myeloid leukemia (AML) represents a heterogeneous blood malignancy and is the most common and severe acute leukemia in adult. The METTL gene family is increasingly being recognized as involved in cancer progression. The aim of the study is to elaborate on the specific role of METTL11A in AML.</p><p><strong>Methods: </strong>In this research, cell viability, transwell assay, and scratch wound assay were utilized to assess cell proliferation and migration in AML cells. Western blot was used to determine the expression of proteins and the activation of signal pathway. Virtual screening was performed to obtain potential inhibitors of METTL11A.</p><p><strong>Results: </strong>Our findings indicated that METTL11A expression levels were strongly associated with AML patients' prognosis. Overexpressed METTL11A by constructing stable cell lines promoted proliferation and migration in AML cells. Conversely, knockdown of METTL11A inhibited cell viability and migration. Through gene sets enrichment analysis, we validated the inactivated p38-mitogen-activated protein kinase (MAPK) pathway under silenced METTL11A expression. In high throughput molecular docking, S-Adenosyl-L-methionine disulfate tosylate was predicted to bind METTL11A, which was validated to inhibit cell proliferation and migration.</p><p><strong>Conclusions: </strong>The results suggested that METTL11A is a novel biomarker and therapeutic target in AML, which is mediated by suppressed MAPK pathway.</p>\",\"PeriodicalId\":23216,\"journal\":{\"name\":\"Translational cancer research\",\"volume\":\"14 8\",\"pages\":\"4561-4573\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-08-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432591/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tcr-2025-602\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tcr-2025-602","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/28 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
METTL11A serves as a novel therapeutic target for acute myeloid leukemia through regulation of the p38-MAPK pathway.
Background: Acute myeloid leukemia (AML) represents a heterogeneous blood malignancy and is the most common and severe acute leukemia in adult. The METTL gene family is increasingly being recognized as involved in cancer progression. The aim of the study is to elaborate on the specific role of METTL11A in AML.
Methods: In this research, cell viability, transwell assay, and scratch wound assay were utilized to assess cell proliferation and migration in AML cells. Western blot was used to determine the expression of proteins and the activation of signal pathway. Virtual screening was performed to obtain potential inhibitors of METTL11A.
Results: Our findings indicated that METTL11A expression levels were strongly associated with AML patients' prognosis. Overexpressed METTL11A by constructing stable cell lines promoted proliferation and migration in AML cells. Conversely, knockdown of METTL11A inhibited cell viability and migration. Through gene sets enrichment analysis, we validated the inactivated p38-mitogen-activated protein kinase (MAPK) pathway under silenced METTL11A expression. In high throughput molecular docking, S-Adenosyl-L-methionine disulfate tosylate was predicted to bind METTL11A, which was validated to inhibit cell proliferation and migration.
Conclusions: The results suggested that METTL11A is a novel biomarker and therapeutic target in AML, which is mediated by suppressed MAPK pathway.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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