Long noncoding RNA (lncRNA) FOXC2-AS1 has been reported to act as an oncogene in multiple human cancers. However, the clinical significance, functional role and underlying mechanism of FOXC2-AS1 in gastric cancer (GC) remains largely unknown. Here, we found that FOXC2-AS1 expression was significantly elevated in GC tissues and cells, and overexpression of FOXC2-AS1 indicated advanced TNM stage and shorter overall survival in GC patients. Functionally, knockdown of FOXC2-AS1 attenuated the proliferation, migration and invasion of GC cells, whereas overexpression of FOXC2-AS1 showed the opposite effects. Further investigation revealed that FOXC2-AS1 interacted with FOXC2 mRNA and repressed its degradation. FOXC2-AS1 recruited RNA methyltransferase NSUN2 to FOXC2 mRNA, increasing its m⁵C level and association with YBX1. Taken together, our findings suggested that FOXC2-AS1 acted as an oncogenic lncRNA by stabilizing FOXC2 mRNA in an m⁵C-dependent manner, which may provide a novel therapeutic target for GC.

据报道，长链非编码 RNA (lncRNA) FOXC2-AS1 在多种人类癌症中充当癌基因。然而，FOXC2-AS1在胃癌（GC）中的临床意义、功能作用和潜在机制仍然很大程度上未知。在这里，我们发现 FOXC2-AS1 在 GC 组织和细胞中的表达显着升高，并且 FOXC2-AS1 的过表达表明 GC 患者的 TNM 晚期和较短的总生存期。在功能上，FOXC2-AS1 的敲低减弱了 GC 细胞的增殖、迁移和侵袭，而 FOXC2-AS1 的过表达则显示出相反的效果。进一步的研究表明，FOXC2-AS1 与 FOXC2 mRNA 相互作用并抑制其降解。FOXC2-AS1 将 RNA 甲基转移酶 NSUN2 募集到 FOXC2 mRNA，增加其 m ⁵C 级和与 YBX1 的关联。总之，我们的研究结果表明，FOXC2-AS1 通过以 m ⁵ C 依赖性方式稳定 FOXC2 mRNA 充当致癌 lncRNA，这可能为 GC 提供新的治疗靶点。