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The Fragile X Mental Retardation 1 (FMR1) gene has been implicated in the development and progression of various tumors, but its role in gastric cancer remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed pan-cancer expression analysis of FMR1 using the TIMER2.0 platform, and evaluated its differential expression in gastric cancer versus normal gastric tissues in the TCGA cohort. FMR1 expression was validated by qRT-PCR, Western blotting, and immunohistochemistry. Using R software and clinical samples to evaluate the association between FMR1 expression levels and clinicopathological factors in gastric cancer patients, and to analyze patient survival curves. The relationship between FMR1 expression and tumor immune infiltration was analyzed via the TISIDB database, and after co-culture, cytokine secretion by CD4\u207a T cells was assessed using ELISA following FMR1 knockdown in tumor cells. Functional enrichment analyses of FMR1 and its interacting genes were performed. Single-cell transcriptomics was used to extend the interpretation of intratumoral lineages and states. Malignant epithelial populations were identified using inferCNV, and these cells were subsequently stratified by FMR1 expression for GSVA. We measured FMR1 expression in control and FMR1 knockdown gastric cancer cells, performed proliferation, migration, and invasion assays to investigate the biological effects of FMR1 in gastric cancer. Mechanistic insights were further explored through co-immunoprecipitation, cycloheximide chase, proteasome inhibition, and rescue assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FMR1 was significantly overexpressed in gastric cancer tissues compared to normal gastric mucosa, with high expression levels associated with poor prognosis. The differential expression of FMR1 in gastric cancer was strongly associated with the activity of multiple immune cell types within the tumor microenvironment. Functional assays further demonstrated that FMR1 knockdown suppressed cytokine secretion by CD4\u207a T cells. The expression level of FMR1 in malignant epithelial cells is higher than that in the non\u2014malignant group, and the high\u2014expression group of FMR1 in malignant cells shows a consistent increase in the Hallmark gene sets directly related to stem cell like phenotype, chemotherapy resistance, and immune evasion. Knockdown of FMR1 suppressed gastric cancer cell proliferation, migration, and invasion, while mechanistic studies indicated that FMR1 positively regulates c-MYC expression to drive these phenotypes. And we found that FMR1 interacted with c-MYC at the protein level and stabilized c-MYC by suppressing its proteasomal degradation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that FMR1 promotes gastric cancer cell proliferation, migration, and invasion through c-MYC signaling, suggesting that FMR1 may serve as a potential prognostic biomarker and therapeutic target for gastric cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-07140-8","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T10:09:57Z","timestamp":1762164597000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Fragile X mental retardation 1 gene FMR1 promotes proliferation, migration, and invasion of gastric cancer cells via c-MYC"],"prefix":"10.1186","volume":"23","author":[{"given":"Yiqian","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangjie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingtong","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidong","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhou","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenglei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"issue":"1","key":"7140_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13045-023-01451-3","volume":"16","author":"WL Guan","year":"2023","unstructured":"Guan WL, He Y, Xu RH. 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For immunohistochemistry experiments, this study is a retrospective study. It mainly conducts data analysis based on the medical records and relevant laboratory test results retained during previous clinical diagnosis and treatment processes. The research content does not involve any interventional operations on patients, nor does it affect the diagnosis and treatment process and results of patients. All the included data will be anonymized before analysis, not containing information that can identify an individual, such as the patient's name, ID number, address, and phone number, to ensure patient privacy and data security. The data is only used for the purpose of this study and will not be used for other purposes without permission. Since this study does not involve direct contact with patients, it will not cause any physical or psychological impact on them. Moreover, as the research objects are previous data and it is impossible to contact each patient individually to obtain informed consent, it is not appropriate to obtain informed consent from patients on a case\u2014by\u2014case basis for this study. Considering the low risk of the study, the anonymity of the data, and the minimal impact on the rights and interests of the subjects, we have applied to the ethics committee for exemption from informed consent and the application has been approved. Regarding the extraction of human peripheral blood CD4\u2009+\u2009T cells, we have obtained informed consent from volunteers and passed the ethical review of the ethics committee.","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 declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1210"}}