Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination-mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment.

中文翻译：

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m6A 修饰介导的 lncRNA TP5​​3TG1 通过调节 CIP2A 稳定性抑制胃癌进展

长链非编码 RNA (lncRNA) 与多种类型的癌症有关。然而，许多 lncRNA 在肿瘤进展中的确切作用仍不清楚。在这项研究中，我们发现 lncRNA TP5​​3TG1 的表达在胃癌 (GC) 中下调，并起到肿瘤抑制因子的作用。此外，低 TP53TG1 表达与 GC 患者的低生存率显着相关。TP53TG1抑制GC细胞的增殖、转移和细胞周期进程，同时促进其凋亡。m6A 修饰位点在 TP53TG1 上非常丰富，去甲基化酶 ALKBH5 会降低 TP53TG1 的稳定性并下调其表达。TP53TG1 与蛋白磷酸酶 2A (CIP2A) 的癌性抑制剂相互作用并触发其泛素化介导的降解，从而抑制 PI3K/AKT 通路。