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bioRxiv · 10.1101/2025.01.25.634861

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

Sun, X.·Han, S.·Liu, K.·Si, Y.·Xuan, M.·Zhang, R.·Jiao, J.·Liu, T.·Yu, W.·Wang, J.
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Abstract

Gastric cancer (GC) is a widespread and deadly malignancy among global digestive tract tumors, alarmingly ranked the fifth most common cancer in terms of incidence and mortality. This study used immunohistochemistry and RT-qPCR to reveal a significant upregulation of YTHDF3 expression in GC tissues compared with that of adjacent normal tissues. This increased expression of YTHDF3 was closely associated with the incidence of lymph node metastasis and the progression to more advanced TNM stages. In vitro experiments demonstrated that YTHDF3 was crucial in promoting the aggressive characteristics of GC cells by enhancing their ability to proliferate, migrate, and invade, while simultaneously inhibiting apoptosis. The role of YTHDF3 in the progression of GC was further confirmed using the BALB/c nude mice subcutaneous tumor model, which showed a slowed tumor growth after YTHDF3 knockdown. This study further confirmed through Co-IF RIP-qPCR, western blotting, and rescue studies that YTHDF3 promotes GC progression by targeting NEK7 to regulate the Wnt/{beta}-catenin signaling pathway. In conclusion, our pivotal findings highlight the YTHDF3/NEK7/Wnt/{beta}-catenin axis as a promising and accessible therapeutic target for the development of new treatments aimed at improving clinical outcome of patients with GC.

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Sun, X., Han, S., Liu, K., Si, Y., Xuan, M., Zhang, R., Jiao, J., Liu, T., Yu, W., Wang, J.. 2025-01-27. YTHDF3 promotes the progression of gastric cancer by activating Wnt/β-catenin signaling pathway via targeting NEK7. https://doi.org/10.1101/2025.01.25.634861

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