HBXIP promotes gastric cancer via METTL3-mediated MYC mRNA m6A modification.

Gastric cancer (GC) is one of the most common malignancies worldwide with limited treatment options and distinct geographical distribution even in countries such as China. Genetic alterations during its carcinogenesis need urgent elucidation. In this study, we propose an intriguing hypothesis that the hepatitis B X-interacting protein (HBXIP) may function as an oncogene in GC. We harvested 45 GC tissues and matched the paracancerous tissues. The c-myc proto-oncogene (MYC) N6-methyladenosine (m6A) mRNA methylation was detected by m6A RNA immunoprecipitation and dot-blot assays. Expressions of HBXIP, methyltransferase like 3 (METTL3) and MYC were all determined to be upregulated in both GC tissues and cells. Silencing HBXIP led to a decreased expression of METTL3, which inhibited GC cell proliferation, migration and invasion while promoting their apoptosis. Furthermore, METTL3 enhanced MYC m6A methylation and increased MYC translation, which could potentiate the proliferation, migration and invasion of GC cells. Finally, the HBXIP knockdown impeded the tumorigenicity of GC cells in vivo. Based on the findings of this study, we conclude that HBXIP plays an oncogenic role in GC via METTL3-mediated MYC mRNA m6A modification. The study offers a comprehensive understanding of HBXIP as a potential therapeutic target to limit GC progression.