RNA modification-related genes illuminate prognostic signature and mechanism in esophageal squamous cell carcinoma

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 in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 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. [Display omitted] •A five-RMG-based prognostic signature for ESCC was developed•m5C tRNA modification regulates translation efficiency in a codon-dependent manner•NSUN6 inhibits ESCC progression via modulating CDH1 mRNA translation Oncology; Biological sciences; Genetics; Molecular biology; Cancer systems biology