PURPOSE The expression and regulatory mechanism of NSUN6 in lung cancer are still unclear. Our study explored whether NSUN6 mediates progression of lung cancer by affecting NM23-H1 expression in an m5C-dependent manner. METHODS qRT-PCR, CCK-8, colony formation, transwell and western blot analysis were employed to probe the impact of NSUN6 on lung cancer cell proliferation, migration and epithelial-mesenchymal transition (EMT). RMVar database was utilized to forecast the downstream genes of NSUN6. The mode of interaction between NSUN6 and NM23-H1 was determined by dot blot, luciferase assay, m5C RIP and cell function assays. The effect of NSUN6 expression on tumor growth was verified in vivo. RESULTS Expression of NSUN6 was reduced in lung cancer cells and over-expression of NSUN6 restricted the proliferation of lung cancer cells, migration and EMT. NSUN6 regulated NM23-H1 expression by modifying the 3'-UTR of NM23-H1 mRNA through m5C, and inhibited lung cancer cell proliferation, migration and EMT. In vivo experiments also showed that over-expression of NSUN6 inhibited the occurrence of lung cancer. CONCLUSION NSUN6 regulates NM23-H1 expression in an m5C-dependent manner to effect EMT in lung cancer. Thus, NSUN6 may considered as a potential therapeutic target for lung cancer.

中文翻译：

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NSUN6 以 m5C 方式调节 NM23-H1 表达，从而影响肺癌中的上皮间质转化。

目的 NSUN6在肺癌中的表达和调控机制仍不清楚。我们的研究探讨了 NSUN6 是否通过以 m5C 依赖性方式影响 NM23-H1 表达来介导肺癌进展。方法采用qRT-PCR、CCK-8、集落形成、transwell和western blot分析探讨NSUN6对肺癌细胞增殖、迁移和上皮间质转化（EMT）的影响。利用RMVar数据库预测NSUN6的下游基因。通过斑点印迹、荧光素酶测定、m5C RIP 和细胞功能测定确定 NSUN6 和 NM23-H1 之间的相互作用模式。NSUN6表达对肿瘤生长的影响在体内得到验证。结果 肺癌细胞中NSUN6的表达降低，NSUN6的过表达限制了肺癌细胞的增殖、迁移和EMT。NSUN6通过m5C修饰NM23-H1 mRNA的3'-UTR来调节NM23-H1表达，抑制肺癌细胞增殖、迁移和EMT。体内实验还表明，NSUN6的过表达可抑制肺癌的发生。结论 NSUN6 以 m5C 依赖性方式调节 NM23-H1 表达，从而影响肺癌的 EMT。因此，NSUN6可能被认为是肺癌的潜在治疗靶点。