Han Hui, Sun Yucong, Wei Wei, Huang Zixin, Cheng Maosheng, Qiu Hongshen, Wang Juan, Zheng Siyi, Liu Lianlian, Zhang Qiang, Zhang Canfeng, Ma Jieyi, Guo Siyao, Wang Zhaoyu, Li Zhenpeng, Jiang Xu, Lin Shuibin, Liu Qianwen, Zhang Shuishen
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
iScience. 2024 Feb 24;27(3):109327. doi: 10.1016/j.isci.2024.109327. eCollection 2024 Mar 15.
Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression and , whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA mC modifications selectively enhance the translation efficiency of mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.
新兴研究已证明RNA修饰与多种癌症之间的联系，而RNA修饰相关基因（RMGs）在食管鳞状细胞癌（ESCC）中的预测价值和功能机制仍不清楚。在此，我们基于五个RMGs建立了ESCC的预后特征。对ESCC临床样本的分析进一步验证了该预后特征的预后能力。此外，我们发现敲低NSUN6会促进ESCC进展，而NSUN6的过表达则会抑制ESCC细胞的恶性表型。从机制上讲，NSUN6介导的tRNA mC修饰以密码子依赖性方式选择性地提高mRNA的翻译效率。挽救实验表明，E-钙黏蛋白是介导NSUN6在ESCC进展调控中功能的重要下游靶点。这些发现为ESCC与RMGs之间的联系提供了更多见解，并为ESCC的管理和治疗提供了潜在策略。
