Genes and Diseases (Nov 2023)

PRMT1 promotes the proliferation and metastasis of gastric cancer cells by recruiting MLXIP for the transcriptional activation of the β-catenin pathway

  • Feng Wang,
  • Shitong Chen,
  • Shihan Peng,
  • Xujun Zhou,
  • Houyi Tang,
  • Hanghua Liang,
  • Xi Zhong,
  • He Yang,
  • Xiaoxue Ke,
  • MuHan Lü,
  • Hongjuan Cui

Journal volume & issue
Vol. 10, no. 6
pp. 2622 – 2638

Abstract

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Protein arginine methyltransferase 1 (PRMT1), a type I PRMT, is overexpressed in gastric cancer (GC) cells. To elucidate the function of PRMT1 in GC, PRMT1 expression in HGC-27 and MKN-45 cells was knocked down by short hairpin RNA (shRNA) or inhibited by PRMT1 inhibitors (AMI-1 or DCLX069), which resulted in inhibition of GC cell proliferation, migration, invasion, and tumorigenesis in vitro and in vivo. MLX-interacting protein (MLXIP) and Kinectin 1 (KTN1) were identified as PRMT1-binding proteins. PRMT1 recruited MLXIP to the promoter of β-catenin, which induced β-catenin transcription and activated the β-catenin signaling pathway, promoting GC cell migration and metastasis. Furthermore, KTN1 inhibited the K48-linked ubiquitination of PRMT1 by decreasing the interaction between TRIM48 and PRMT1. Collectively, our findings reveal a mechanism by which PRMT1 promotes cell proliferation and metastasis mediated by the β-catenin signaling pathway.

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