ArticleFrontiers in immunology2026
CircNF1 promotes gastric cancer metastasis by stabilizing HMGA2 mRNA through IGF2BP1 interaction.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Gastric cancer (GC) is the fifth most common malignancy worldwide, with metastasis being the primary cause of mortality. Although circular RNAs (circRNAs) are implicated in GC pathogenesis, their specific roles in metastasis remain unclear. This study was designed to investigate the functional significance and underlying molecular mechanisms of circNF1 in GC metastasis. Methods: The expression of circNF1 was assessed in GC tissues and paired adjacent normal tissues using Results: Overexpression of circNF1 significantly enhanced GC cell migration in vitro and lung metastasis in vivo, whereas knockdown of circNF1 suppressed these metastatic phenotypes. Mechanistically, circNF1 was found to interact directly with IGF2BP1, thereby stabilizing HMGA2 mRNA and promoting its expression. Furthermore, ZNF460 was identified as a transcriptional activator of the NF1 host gene, which in turn upregulated circNF1 expression. Discussion: Our findings demonstrate that ZNF460-mediated upregulation of circNF1 drives GC metastasis by acting as a molecular scaffold to interact with IGF2BP1 and stabilize HMGA2 mRNA. This study not only elucidates a novel regulatory axis in GC metastasis but also identifies circNF1 as a promising prognostic biomarker and potential therapeutic target for the treatment of metastatic GC.
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