2. Academic Validation
  3. PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C-Myc Feedback Loop

PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C-Myc Feedback Loop

  • MedComm (2020). 2025 May 15;6(6):e70150. doi: 10.1002/mco2.70150.
Fan Yang 1,  Ping Song 2 3 4,  Zhaofeng Xiao 5,  Renyi Su 6,  Xin Fang 1,  Yichao Wu 7,  Xiao Xu 7 8 9,  Kai Wang 9
Affiliations

Affiliations

  • 1 Department of Vascular Surgery Affiliated Hangzhou First People's Hospital School of Medicine Westlake University Hangzhou China.
  • 2 Department of Gastroenterology Affiliated Hangzhou First People's Hospital School of Medicine Westlake University Hangzhou China.
  • 3 Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province Hangzhou China.
  • 4 Hangzhou Institute of Digestive Diseases Hangzhou China.
  • 5 The Fourth School of Clinical Medicine Zhejiang Chinese Medical University Hangzhou China.
  • 6 School of Clinical Medicine Zhejiang University Hangzhou China.
  • 7 Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College Hangzhou China.
  • 8 NHC Key Laboratory of Combined Multi-Organ Transplantation Hangzhou China.
  • 9 School of Clinical Medicine Hangzhou Medical College Hangzhou China.
PMID: 40384988 DOI: 10.1002/mco2.70150
Abstract

The oncogenic role and underlying mechanism of PRMT5 in pancreatic ductal adenocarcinoma (PAAD) remained to be elucidated. In this study, we aimed to investigate the oncogenic role, underlying molecular mechanisms, and potential therapeutic value of PRMT5 in PAAD. PRMT5 was significantly upregulated in pancreatic Cancer than adjacent nontumor pancreas, which was positively correlated with poor prognosis. Genetic and pharmacological inhibition of PRMT5 suppressed PAAD proliferation in vitro and in vivo, exhibiting promising therapeutic effect in vivo. Mechanistically, PRMT5 directly bound to the promoter region of c-Myc and activated its transcription. Transcriptionally activated c-Myc in turn inhibited proteasome-mediated degradation of PRMT5 and enhanced its protein stability, resulting in increased PRMT5 expression. The maintained PRMT5 further enhanced the transcription of c-Myc. In conclusion, PRMT5 forms a positive feedback loop with c-Myc to promote the proliferation of pancreatic Cancer. Targeting this oncogenic communication may represent a novel and potential therapeutic approach for pancreatic Cancer.

Keywords

PRMT5; c‐Myc; pancreatic cancer; positive feedback loop; proliferation; therapeutic targets.

Figures
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  • HY-15260
    99.76%, CDK Inhibitor
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