Abstract
Purpose
Wilms tumor 1 associated protein (WTAP) is a key RNA n6-methyladenosine (m6A) methylase, which predicts the occurrence of many diseases, such as liver fibrosis formation, coordinating cancer stem cell function, and promoting tumor development. Gastric cancer (GC) is one of the most common malignant tumors worldwide. However, the role of WTAP in GC development and drug resistance remains unclear.
Methods
Biological methods and data analysis were used to investigate the expression of WTAP in gastric carcinoma tissue. The expression of transforming growth factor-beta (TGF-β) and epithelial mesenchymal transition (EMT) in GC cells were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) with WTAP overexpression cell lines and WTAP knockout cell lines. Gradient concentrations of cisplatin (DDP), gradient cyclophosphamide (CTX), or radiation X-rays were added to WTAP overexpression cell lines and WTAP knockdown cell lines to observe the change of cell viability after radiotherapy and chemotherapy treatment.
Results
The expression of WTAP in gastric carcinoma tissue significantly increased as determined by bioinformatics analysis, and a high expression of WTAP was closely associated with poor prognosis of gastric cancer patients. Overexpression of WTAP promoted migration and EMT of GC cells and promoted the expression of TGF-β and the stability of mRNA. WTAP knockdown inhibited migration of GC cells and decreased TGF-β expression and stability of mRNA. In addition, WTAP promoted multiple chemotherapy resistance and radiotherapy resistance in GC.
Conclusions
WTAP is a potential predictive biomarker for GC. Our findings revealed a novel mechanism by which WTAP regulates chemoradiotherapy resistance, extending the understanding of the m6A machinery in TGF-β induced EMT and metastasis in GC.
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Data availability
The datasets and materials used in the current study are available from the corresponding author upon request.
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Acknowledgements
The authors are grateful to all of the laboratory members for their assistance. Thanks to Dr. Edward C. Mignot, Shandong University, for linguistic advice.
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This study was supported by the Gansu Provincial People’s Hospital National Scientific Research project cultivation plan (Fund 19SYPYA-7).
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Yu Liu: Cultured cells, performed statistical analysis, performed the experiments, designed the study and made a major contribution to writing the article. Mingxu Da: Designed the study and made a major contribution to writing the article. All authors read and approved the final version.
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Liu, Y., Da, M. Wilms tumor 1 associated protein promotes epithelial mesenchymal transition of gastric cancer cells by accelerating TGF-β and enhances chemoradiotherapy resistance. J Cancer Res Clin Oncol 149, 3977–3988 (2023). https://doi.org/10.1007/s00432-022-04320-7
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DOI: https://doi.org/10.1007/s00432-022-04320-7