binds to to activate the cyclic guanosine monophosphate-protein kinase G pathway, promoting gastric cancer progression.

[BACKGROUND] N-methyladenosine (mA) exerts a pro-carcinogenic effect in diverse cancers. The relationship between mA-reading protein and gastric cancer (GC) has not yet been fully elucidated.

[AIM] To investigate the molecular mechanisms of in GC carcinogenesis and progression and thus provide a rationale for novel therapeutic strategies.

[METHODS] Expression levels of in GC were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blot (WB), and immunohistochemistry, and their associations with patients' clinicopathological characteristics were analyzed. The role of in GC was investigated using cellular functional assays and subcutaneous xenograft models, and its downstream targets and signaling pathways were identified using high-throughput sequencing, bioinformatics analysis, RNA immunoprecipitation qPCR, dual luciferase reporter assay, qRT-PCR, and WB. The mechanism of in GC was validated WB and rescue and inhibition experiments.

[RESULTS] was highly expressed in GC and associated with diffuse-type GC, incidence of lymph node metastasis, advanced tumor node metastasis stage, and deeper tumor invasion depth. experiments demonstrated that promoted proliferation, migration, and invasiveness of GC cells, while inhibiting apoptosis and augmenting intracellular levels of glucose metabolism. experiments revealed that contributes to the growth of GC. Mechanistically, recognized and bound to the mA site at position 1427 on messenger RNA, thereby increasing protein expression of , and further activated the downstream cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway to modulate various biological functions of GC cells and promote progression of GC. Furthermore, treatment with a selective PKG inhibitor KT5823 significantly suppressed the proliferative capacity of GC cells.

[CONCLUSION] increases protein expression in an mA-dependent manner, activates the cGMP-PKG signaling pathway, and promotes GC progression. Targeting of the //cGMP-PKG axis could thus represent a promising therapeutic modality for GC.