2. Academic Validation
  3. NSUN5 promotes tumorigenic phenotypes through the WNT signaling pathway and immunosuppression of CD8+ T cells in gastric cancer

NSUN5 promotes tumorigenic phenotypes through the WNT signaling pathway and immunosuppression of CD8+ T cells in gastric cancer

  • Cell Signal. 2024 Dec:124:111475. doi: 10.1016/j.cellsig.2024.111475.
Shuhao Liu 1,  Yong Liu 2,  Yijun Zhou 3,  Gaoshui Xia 4,  Haibo Liu 1,  Yu Zeng 5,  Zhihui Pei 5,  Jing Cao 1,  Guifang Jing 1,  Hailin Zou 6,  Chuanwen Liao 1
Affiliations

Affiliations

  • 1 Gastrointestinal Hernia Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No.152 Aiguo Road, Nanchang City 330006, Jiangxi Province, PR China.
  • 2 Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, PR China.; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Shenzhen 518107, Guangdong, PR China.
  • 3 School of Medicine, Sun Yat-sen University (Shenzhen), Shenzhen 518107, China.
  • 4 Nanchang Medical College. No. 689, Huiren Avenue, Nanchang Xiaolan Economic And Technological Development Zone, Nanchang City 330052, Jiangxi Province, PR China.
  • 5 Gastrointestinal Hernia Surgery, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, No.152 Aiguo Road, Nanchang City 330006, Jiangxi Province, PR China; Jiangxi Medical College, Nanchang University, No. 461, Bayi Avenue, Nanchang City 330006, Jiangxi Province, PR China.
  • 6 Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Shenzhen 518107, Guangdong, PR China. Electronic address: kylcw345@163.com.
PMID: 39428025 DOI: 10.1016/j.cellsig.2024.111475
Abstract

NSUN5, a key member of the M5C methylation family, plays a significant role in fundamental biological processes like cell proliferation and differentiation. However, its specific function and mechanisms in gastric Cancer remain insufficiently understood. Initially, we examined NSUN5's differential expression in gastric Cancer versus normal tissues, along with survival trends, associated signaling pathways, and immune infiltration using the TCGA database. Subsequently, we conducted immunohistochemistry experiments to assess NSUN5 expression in gastric Cancer tissues. Gain-and loss-of-function experiments were carried out to investigate NSUN5's impact on the proliferation, stemness, and migratory capabilities of gastric Cancer cells, as well as the expression of vital proteins in pertinent signaling pathways. Our findings demonstrate that NSUN5 is not only overexpressed in gastric Cancer tissues, but also positively associated with tumor stage and inversely linked with patient prognosis. NSUN5 promotes the in vitro proliferation, stemness, and migration of gastric Cancer cells, and the in vivo growth of these cells, chiefly through the activation of the Wnt/β-catenin signaling pathway. Additionally, NSUN5 appears to diminish the infiltration of CD8+ T cells in gastric Cancer, contributing to immune evasion. In conclusion, NSUN5 functions as a proto-oncogene in the progression of gastric Cancer and may serve as a potential therapeutic target.

Keywords

Gastric cancer; Immunity; NSUN5; Oncogene; WNT/β-catenin signaling pathway.

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