2. Academic Validation
  3. PRMT1 methylation of WTAP promotes multiple myeloma tumorigenesis by activating oxidative phosphorylation via m6A modification of NDUFS6

PRMT1 methylation of WTAP promotes multiple myeloma tumorigenesis by activating oxidative phosphorylation via m6A modification of NDUFS6

  • Cell Death Dis. 2023 Aug 9;14(8):512. doi: 10.1038/s41419-023-06036-z.
Yachun Jia 1 2,  Xiao Yu 1,  Rui Liu 2,  Luyi Shi 3,  Hua Jin 1 3,  Dan Yang 1,  Xiaofeng Zhang 1,  Ying Shen 2,  Yuandong Feng 2,  Peihua Zhang 1 2,  Yi Yang 1 3,  Linlin Zhang 1 3,  Pengyu Zhang 2,  Zongfang Li 4 5,  Aili He 6 7,  Guangyao Kong 8 9 10 11
Affiliations

Affiliations

  • 1 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
  • 2 Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
  • 3 Precision Medical Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
  • 4 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. lzf2568@xjtu.edu.cn.
  • 5 Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. lzf2568@xjtu.edu.cn.
  • 6 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. heaili@xjtu.edu.cn.
  • 7 Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. heaili@xjtu.edu.cn.
  • 8 National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. konggy@xjtu.edu.cn.
  • 9 Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. konggy@xjtu.edu.cn.
  • 10 Precision Medical Institute, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. konggy@xjtu.edu.cn.
  • 11 Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China. konggy@xjtu.edu.cn.
PMID: 37558663 DOI: 10.1038/s41419-023-06036-z
Abstract

Epigenetic modifications play important roles during the pathogenesis of multiple myeloma (MM). Herein, we found that protein arginine methyltransferase 1 (PRMT1) was highly expressed in MM patients, which was positively correlated with MM stages. High PRMT1 expression was correlated with adverse prognosis in MM patients. We further showed that silencing PRMT1 inhibited MM proliferation and tumorigenesis in vitro and in vivo. Mechanistically, we revealed that the knockdown of PRMT1 reduced the Oxidative Phosphorylation (OXPHOS) of MM cells through NDUFS6 downregulation. Meanwhile, we identified that WTAP, a key component of the m6A methyltransferase complex, was methylated by PRMT1, and NDUFS6 was identified as a bona fide m6A target of WTAP. Finally, we found that the combination of PRMT1 Inhibitor and bortezomib synergistically inhibited MM progression. Collectively, our results demonstrate that PRMT1 plays a crucial role during MM tumorigenesis and suggeste that PRMT1 could be a potential therapeutic target in MM.

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