YTHDF3 promotes the progression of gastric cancer by activating Wnt/β-catenin signaling pathway via targeting NEK7

Gastric cancer is a widespread and deadly malignancy among global digestive tract tumors, alarmingly ranking as the fifth most common cancer in terms of incidence and mortality. Our research, utilizing immunohistochemistry and qRT-PCR, revealed a significant upregulation of YTHDF3 in gastric cancer tissues compared to adjacent non-cancerous tissues. This increased expression of YTHDF3 was found to be closely associated with the incidence of lymph node metastasis and the progression to more advanced TNM stages in patients. In vitro experiments demonstrated that YTHDF3 is crucial in promoting the aggressive characteristics of gastric cancer cells by enhancing their ability to proliferate, migrate, and invade, while simultaneously inhibiting apoptosis. The role of YTHDF3 in the progression of gastric cancer was further confirmed by nude mouse subcutaneous tumor model, which showed slowed tumor growth upon YTHDF3 knockdown. This study further confirms through a series of experiments including Co-IP, Co-IF, Western blot, and rescue studies that YTHDF3 promotes the progression of gastric cancer by targeting NEK7 to regulate the Wnt/β-catenin signaling pathway. These pivotal findings highlight the YTHDF3/NEK7/Wnt/β-catenin axis as a promising and accessible therapeutic target for developing new treatments aimed at enhancing the outcomes for gastric cancer patients.