Further investigation on several outstanding issues, e.g. These available chemical compounds, as well as other approaches that target core components of the RNA m 6A pathway hold promises for clinical translational to treat human GI cancers. From a historical perspective, milestone findings in m 6A machinery are integrated with a timeline of developing m 6A targeting compounds. In this review, we comprehensively summarize recent advances in this field and highlight research findings that documented key roles of RNA m 6A modification in governing hallmarks of GI cancers. Therefore, regulators and effectors of m 6A, as well as their modified substrates, represent a novel class of molecular targets for cancer treatments. Through these regulatory mechanisms, m 6A dictates gene expression in a dynamic and reversible manner and may play oncogenic, tumor suppressive or context-dependent roles in GI tumorigenesis. As an important layer of epigenetic regulation, RNA N6-Methyladenosine (m 6A) modification is recently linked to various biological hallmarks of cancer by orchestrating RNA metabolism, including RNA splicing, export, translation, and decay, which is partially involved in a novel biological process termed phase separation. However, molecular targeted therapies are still lacking, leading to poor treatment efficacies. Gastrointestinal (GI) cancer is one of the most common malignancies, and a leading cause of cancer-related death worldwide.
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