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
Affiliations
Hui Han
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author
Yucong Sun
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Wei Wei
Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
Zixin Huang
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Maosheng Cheng
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Hongshen Qiu
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Juan Wang
Division of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Siyi Zheng
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Lianlian Liu
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Qiang Zhang
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Canfeng Zhang
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Jieyi Ma
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Siyao Guo
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Zhaoyu Wang
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Zhenpeng Li
Department of Microsurgery, Orthopedic Trauma and Hand Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Xu Jiang
School of basic medical sciences, Southern Medical University, Guangzhou 510515, China
Shuibin Lin
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China
Qianwen Liu
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; Guangdong Esophageal Cancer Institute, Guangzhou 510080, China; Corresponding author
Shuishen Zhang
Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Corresponding author
Summary: 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.
