PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop
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 up...
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| Format: | Article |
| Language: | English |
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Wiley
2025-06-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.70150 |
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| author | Fan Yang Ping Song Zhaofeng Xiao Renyi Su Xin Fang Yichao Wu Xiao Xu Kai Wang |
| author_facet | Fan Yang Ping Song Zhaofeng Xiao Renyi Su Xin Fang Yichao Wu Xiao Xu Kai Wang |
| author_sort | Fan Yang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-382a5bba2197481e8f0d49d0b0ed0aa5 |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-382a5bba2197481e8f0d49d0b0ed0aa52025-08-20T03:39:28ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70150PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback LoopFan Yang0Ping Song1Zhaofeng Xiao2Renyi Su3Xin Fang4Yichao Wu5Xiao Xu6Kai Wang7Department of Vascular Surgery Affiliated Hangzhou First People's Hospital School of Medicine Westlake University Hangzhou ChinaDepartment of Gastroenterology Affiliated Hangzhou First People's Hospital School of Medicine Westlake University Hangzhou ChinaThe Fourth School of Clinical Medicine Zhejiang Chinese Medical University Hangzhou ChinaSchool of Clinical Medicine Zhejiang University Hangzhou ChinaDepartment of Vascular Surgery Affiliated Hangzhou First People's Hospital School of Medicine Westlake University Hangzhou ChinaDepartment of Hepatobiliary Pancreatic and Minimal Invasive Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College Hangzhou ChinaDepartment of Hepatobiliary Pancreatic and Minimal Invasive Surgery Zhejiang Provincial People's Hospital (Affiliated People's Hospital) Hangzhou Medical College Hangzhou ChinaSchool of Clinical Medicine Hangzhou Medical College Hangzhou ChinaABSTRACT 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.https://doi.org/10.1002/mco2.70150pancreatic cancerPRMT5c‐Mycpositive feedback loopproliferationtherapeutic targets |
| spellingShingle | Fan Yang Ping Song Zhaofeng Xiao Renyi Su Xin Fang Yichao Wu Xiao Xu Kai Wang PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop MedComm pancreatic cancer PRMT5 c‐Myc positive feedback loop proliferation therapeutic targets |
| title | PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop |
| title_full | PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop |
| title_fullStr | PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop |
| title_full_unstemmed | PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop |
| title_short | PRMT5 Promotes Pancreatic Cancer Tumorigenesis via Positive PRMT5/C‐Myc Feedback Loop |
| title_sort | prmt5 promotes pancreatic cancer tumorigenesis via positive prmt5 c myc feedback loop |
| topic | pancreatic cancer PRMT5 c‐Myc positive feedback loop proliferation therapeutic targets |
| url | https://doi.org/10.1002/mco2.70150 |
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