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FTO promotes gastric cancer progression by modulating MAP4K4 expression via demethylation in an m6A-dependent manner

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Abstract

Gastric cancer (GC) is a serious malignant tumour with a high mortality rate and a poor prognosis. Recently, emerging evidence has suggested that N6-methyladenosine (m6A) modification plays a crucial regulatory role in cancer progression. However, the exact role of m6A regulatory factors FTO in GC is unclear. First, the expression of m6A methylation-related regulatory factors in clinical samples and the clinical data of the corresponding patients were obtained from The Cancer Genome Atlas (TCGA-STAD) dataset, and correlation analysis between FTO expression and patient clinicopathological parameters was subsequently performed. qRT-PCR, immunohistochemistry (IHC) and western blotting (WB) were used to verify FTO expression in GC. CCK-8, EdU, flow cytometry and transwell assays were used to evaluate the effect of FTO on the behaviour of GC cells. Transcriptome sequencing and RNA immunoprecipitation analysis were used to explore the potential regulatory mechanisms mediated by FTO. FTO was highly expressed in GC tissues and cells, and high expression of FTO predicted a worse prognosis than low expression. Functionally, overexpression of FTO promoted the proliferation, migration and invasion of GC cells but inhibited cell apoptosis. Mechanistically, we found that FTO is upregulated in GC and promotes GC progression by modulating the expression of MAP4K4. Taken together, our findings provide new insights into the effects of FTO-mediated m6A demethylation and could lead to the development of new strategies for GC monitoring and aggressive treatment.

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Data availability

Transcriptomic, matched clinical data and MAF files were downloaded from the TCGA database (https://portal.gdc.cancer.gov/).

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81974385).

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China

    Zhe Yin, Xiong Guo, Xiaolong Liang & Ziwei Wang

  2. Department of Thoracic Surgery, Chongqing University Cancer Hospital, Chongqing Cancer Hospital, Chongqing, 400030, People’s Republic of China

    Zhe Yin

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  1. Zhe Yin
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Contributions

ZY and XG designed the study. ZY and XL carried out the experiment. ZY collected and analysed data. ZY and XG wrote and revised the manuscript. ZW was responsible for supervising the study. All authors read and gave final approval of the manuscript.

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Correspondence to Ziwei Wang.

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Yin, Z., Guo, X., Liang, X. et al. FTO promotes gastric cancer progression by modulating MAP4K4 expression via demethylation in an m6A-dependent manner. Med Oncol 41, 120 (2024). https://doi.org/10.1007/s12032-024-02369-7

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