Abstract

BACKGROUND Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide. Ubiquitin-conjugating enzyme E2K (UBE2K), defined as a E2, was involved in various cellular processes. N6-methyladenosine (m6A) is one of the most abundant subtypes of RNA modifications. However, the systematic role of UBE2K and whether UBE2K undergoes m6A modification in GC remains unknown. METHODS The expression and prognosis of UBE2K in GC were analyzed through an online database. RT-qPCR, western blot and IHC were used to test the expression of UBE2K in GC tissues and cells. CCK-8, colony formation, transwell, wound healing and sphere formation assays were conducted to explore UBE2K's function in vitro. The subcutaneous mouse model was implemented to validate UBE2K's role in tumorigenesis. RNA immunoprecipitation, RNA stability experiment, was applied to investigate the molecular mechanism of UBE2K. RESULTS Higher expression of UBE2K was found in GC tissues and predicted worse prognosis. UBE2K enhanced while UBE2K knockdown suppressed the malignant progression of GC cells both in vitro and in vivo. Mechanistically, we found that UBE2K was regulated by m6A modification. WTAP was further revealed as the m6A writer of UBE2K to enhance UBE2K RNA stability. Finally, functional rescue experiments showed that silencing WTAP reversed the oncogenic effects of UBE2K overexpression on GC cells, whereas WTAP attenuated the suppression of GC cells induced by UBE2K knockdown. CONCLUSION Our findings indicated WTAP-mediated m6A regulation of UBE2K and oncogenic function of WTAP/UBE2K axis in GC, providing a promising therapeutic target for GC treatment.