Emerging evidence has demonstrated that N⁶-methyladenosine (m⁶A) and long noncoding RNAs (lncRNAs) are both crucial regulators in gastric cancer (GC) tumorigenesis. However, the interaction of m⁶A and lncRNAs in GC progression are still unclear. Here, our team discovered that lncRNA LINC00958 expression up-regulated in GC tissue and cells. Clinically, high-expression of LINC00958 was clinically correlated to lower survival of GC patients. Functionally, in vitro assays demonstrated that LINC00958 promoted the GC cells' aerobic glycolysis. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) found that there were m⁶A-modificated sites in LINC00958, and moreover m⁶A methyltransferase KIAA1429 catalyzed the m⁶A modification on LINC00958 loci. Moreover, LINC00958 interacted with GLUT1 mRNA via the m⁶A-dependent manner to enhance GLUT1 mRNA transcript stability, thereby positively regulating the aerobic glycolysis of GC. In conclusion, our findings reveal the function and mechanism of KIAA1429-induced LINC00958 in GC, delineating novel understanding of m⁶A-lncRNA in cancer biology.

中文翻译：

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m6A 转移酶 KIAA1429 稳定的 LINC00958 通过靶向 GLUT1 加速胃癌有氧糖酵解

新出现的证据表明，N ⁶ -甲基腺苷 (m ⁶ A) 和长链非编码 RNA (lncRNA) 都是胃癌 (GC) 肿瘤发生中的关键调节因子。然而，m ⁶ A 和 lncRNA 在 GC 进展中的相互作用仍不清楚。在这里，我们的团队发现 lncRNA LINC00958 在 GC 组织和细胞中表达上调。临床上，LINC00958 的高表达在临床上与 GC 患者的较低存活率相关。在功能上，体外试验表明 LINC00958 促进了 GC 细胞的有氧糖酵解。机制上，甲基化 RNA 免疫沉淀测序 (MeRIP-Seq) 发现 LINC00958 中存在 m ⁶ A 修饰位点，此外还有 m ⁶甲基转移酶 KIAA1429 催化 LINC00958 基因座上的 m ⁶ A 修饰。此外，LINC00958通过m ⁶ A依赖性方式与GLUT1 mRNA相互作用，增强GLUT1 mRNA转录稳定性，从而正向调节GC的有氧糖酵解。总之，我们的研究结果揭示了 KIAA1429 诱导的 LINC00958 在 GC 中的功能和机制，描绘了对癌症生物学中 m ^{6 A-lncRNA 的新认识。}