MZF1-AS1/NSUN2 promotes the peritoneal metastasis of gastric cancer by enhancing the stability of RAB13 mRNA.

Peritoneal metastasis (PM) is a major contributor to poor prognosis in advanced gastric cancer (GC), yet its molecular mechanisms remain insufficiently understood. The results of bioinformatic analysis and clinical sample validation reveal that LncRNA MZF1-AS1 is significantly upregulated in GC tissues, particularly in peritoneal metastases, and is associated with worse overall and post-progression survival. MZF1-AS1 enhances malignant phenotypes and PM of GC cells in vitro and in vivo. Mechanistically, RAB13 is demonstrated as a functional effector of MZF1-AS1 via RNA-seq. MZF1-AS1 enhances RAB13 expression by promoting its mRNA stability, thereby facilitating GC cell proliferation, EMT, migration, invasion, and stemness. Further, RNA pulldown and Mass Spectrometry reveal that MZF1-AS1 directly binds to NSUN2. MZF1-AS1 strengthens the interaction between NSUN2 and RAB13 mRNA, promoting NSUN2-mediated m5C modification and stabilizing RAB13 mRNA. Our findings uncover a novel epi-transcriptomic mechanism by which MZF1-AS1 promotes GC progression via NSUN2-dependent m5C methylation of RAB13 mRNA, offering new insights into PM pathogenesis and highlighting potential therapeutic targets for advanced GC.