2. Academic Validation
  3. NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation

NSUN2 modified by SUMO-2/3 promotes gastric cancer progression and regulates mRNA m5C methylation

  • Cell Death Dis. 2021 Sep 9;12(9):842. doi: 10.1038/s41419-021-04127-3.
Yuanbo Hu  # 1 2,  Chenbin Chen  # 1 2,  Xinya Tong  # 2,  Sian Chen 1 2,  Xianjing Hu 1 2,  Bujian Pan 1 2,  Xiangwei Sun 1 2,  Zhiyuan Chen 2,  Xinyu Shi 2,  Yingying Hu 2 3,  Xian Shen 4,  Xiangyang Xue 5 6,  Mingdong Lu 7
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4 Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • 5 Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • 6 Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Collaborative Innovation Center of Gastrointestinal Cancer in Basic Research and Precision Medicine, Wenzhou Key Laboratory of Cancer-related Pathogens and Immunity, Wenzhou Medical University, Wenzhou, China. [email protected].
  • 7 Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China. [email protected].
  • # Contributed equally.
PMID: 34504059 DOI: 10.1038/s41419-021-04127-3
Abstract

The 5-methylcytosine (m5C) RNA methyltransferase NSUN2 is involved in the regulation of cell proliferation and metastasis formation and is upregulated in multiple cancers. However, the biological significance of NSUN2 in gastric Cancer (GC) and the modification of NSUN2 itself have not been fully investigated. Here, we analyzed the expression level of NSUN2 in tissue microarrays containing 403 GC tissues by immunohistochemistry. NSUN2 was upregulated in GC, and that it was a predictor of poor prognosis. NSUN2 promotes the proliferation, migration, and invasion of GC cells in vitro. We also demonstrated that small ubiquitin-like modifier (SUMO)-2/3 interacts directly with NSUN2 by stabilizing it and mediating its nuclear transport. This facilitates the carcinogenic activity of NSUN2. Furthermore, m5C bisulfite sequencing (Bis-seq) in NSUN2-deficient GC cells showed that m5C-methylated genes are involved in multiple cancer-related signaling pathways. PIK3R1 and PCYT1A may be the target genes that participate in GC progression. Our findings revealed a novel mechanism by which NSUN2 functions in GC progression. This may provide new treatment options for GC patients.

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