WTAP-mediated m6A regulation in digestive system cancers: from molecular mechanisms to therapeutic strategies.

Epigenetic modifications, particularly RNA methylation, play a crucial role in cancer progression, and N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. Wilms tumor 1-associated protein (WTAP), a key component of the m6A methyltransferase complex (MTC), regulates m6A modification, influencing RNA stability, translation, and degradation. WTAP dysregulation has been implicated in various malignancies, with particularly significant roles observed across the digestive system cancers, including but not limited to esophageal, gastric, pancreatic, gallbladder, hepatocellular, and colorectal carcinomas. Overexpression of WTAP is frequently associated with poor prognosis, advanced tumor stages, and increased metastatic potential. This review highlights the multifaceted roles and regulatory network of WTAP in digestive system cancers (DSCs) progression, encompassing tumor cell proliferation, migration, invasion, drug resistance, and immune evasion. Targeting WTAP may offer novel therapeutic strategies for overcoming therapy resistance and improving clinical outcomes in digestive system malignancies. Future research should prioritize: (1) validation of these findings in larger, multicenter, and ethnically diverse patient cohorts; (2) comprehensive elucidation of the molecular mechanisms underlying WTAP-mediated regulation in cancer biology; and (3) systematic exploration of its functional consequences in tumor progression and therapy resistance.