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PRMT1 promotes pancreatic cancer growth and predicts poor prognosis

  • Chao Song
  • Tianwei Chen
  • Lan He
  • Ning Ma
  • Jian-ang Li
  • Ye-Fei Rong
  • Yuan Fang
  • Mengmeng Liu
  • Dong XieEmail author
  • Wenhui LouEmail author
Original Paper
  • 3 Downloads

Abstract

Background

Protein arginine methyltransferase 1 (PRMT1) is the founding member of the PRMT family of proteins, whose members catalyze methylation of arginine residues in various proteins. Although several studies have reported upregulation of PRMT1 in various cancer types, the expression pattern and the underlying mechanism of PRMT1 action in pancreatic ductal adenocarcinoma (PDAC) are still unclear.

Methods

Immunohistochemistry staining as well as RT-PCR was used to determine the expression pattern of PRMT1 in clinical PDAC samples. Lentivirus packaging and transfection were employed to construct cell lines with PRMT1 overexpression or knockdown. MTT and crystal violet assays were used to determine the proliferation rates of PDAC cells. β-catenin transcription activity was measured using a TOPFlash assay. PRMT1 binding to the promoter region of CTNNB1 was determined by ChIP-qPCR assay.

Results

Elevated PRMT1 expression was found in PDAC tissue samples compared to noncancerous normal tissues in 41 patients using a real-time PCR assay and in 90 patients using a tissue microarray (TMA) in conjunction with immunohistochemistry. Analysis of the PRMT1 expression data and PDAC clinical features revealed that PRMT1 expression was significantly correlated with PDAC tumor size and prognosis in postoperative patients. Additional functional experiments revealed that PRMT1 expression promoted the growth of pancreatic cancer-derived cells, both in vitro and in vivo. Mechanistically, we found that PRMT1 increased the cellular β-catenin level. We also found that PRMT1 and β-catenin were co-expressed in TCGA and GTEx datasets containing 370 samples.

Conclusions

Collectively, our study provides novel insight into the expression and function of PRMT1 in PDAC and indicates that PRMT1 may serve as a therapeutic target for treating patients with pancreatic ductal adenocarcinoma.

Keywords

Pancreatic cancer PRMT1 Prognosis Proliferation β-catenin 

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant number: 81572294) to Wenhui Lou. We thank professor YZ. Deng for his writing assistance and Dr. H Jiang for proofreading the manuscript.

Compliance with ethical standards

Conflict of interest statement

The authors declare no competing interests.

Supplementary material

13402_2019_435_MOESM1_ESM.pdf (341 kb)
ESM 1 (PDF 341 kb)

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Copyright information

© International Society for Cellular Oncology 2019

Authors and Affiliations

  • Chao Song
    • 1
  • Tianwei Chen
    • 2
    • 3
  • Lan He
    • 4
  • Ning Ma
    • 2
    • 3
  • Jian-ang Li
    • 1
  • Ye-Fei Rong
    • 1
  • Yuan Fang
    • 1
  • Mengmeng Liu
    • 5
  • Dong Xie
    • 2
    • 3
    Email author
  • Wenhui Lou
    • 1
    Email author
  1. 1.Department of Pancreatic Surgery, Zhongshan HospitalFudan UniversityShanghaiChina
  2. 2.Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  3. 3.University of the Chinese Academy of SciencesShanghaiChina
  4. 4.School of Life Science and TechnologyShanghai Tech UniversityShanghaiChina
  5. 5.Department of Gastroenterology, Zhongshan HospitalFudan UniversityShanghaiChina

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