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

Hui Han; Yucong Sun; Wei Wei; Zixin Huang; Maosheng Cheng; Hongshen Qiu; Juan Wang; Siyi Zheng; Lianlian Liu; Qiang Zhang; Canfeng Zhang; Jieyi Ma; Siyao Guo; Zhaoyu Wang; Zhenpeng Li; Xu Jiang; Shuibin Lin; Qianwen Liu; Shuishen Zhang

doi:10.1016/j.isci.2024.109327

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

iScience. 2024 Feb 24;27(3):109327. doi: 10.1016/j.isci.2024.109327. eCollection 2024 Mar 15.

Authors

Hui Han¹, Yucong Sun¹, Wei Wei², Zixin Huang³, Maosheng Cheng¹, Hongshen Qiu¹, Juan Wang⁴, Siyi Zheng¹, Lianlian Liu⁵, Qiang Zhang¹, Canfeng Zhang¹, Jieyi Ma¹, Siyao Guo¹, Zhaoyu Wang¹, Zhenpeng Li⁶, Xu Jiang⁷, Shuibin Lin¹, Qianwen Liu^{8

9}, Shuishen Zhang¹⁰

Affiliations

¹ Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
² Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China.
³ Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
⁴ Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
⁵ Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
⁶ Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
⁷ School of basic medical sciences, Southern Medical University, Guangzhou 510515, China.
⁸ Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510080, China.
⁹ Guangdong Esophageal Cancer Institute, Guangzhou 510080, China.
¹⁰ Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.

Abstract

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.

Keywords: Biological sciences; Cancer systems biology; Genetics; Molecular biology; Oncology.