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

  • Genes Dis. 2023 Mar 28;10(6):2622-2638. doi: 10.1016/j.gendis.2023.02.006.
Feng Wang  1  2 ,  Shitong Chen  1  2 ,  Shihan Peng  1  2 ,  Xujun Zhou  1  2 ,  Houyi Tang  1  2 ,  Hanghua Liang  1  2 ,  Xi Zhong  1  2 ,  He Yang  1  2 ,  Xiaoxue Ke  1  2 ,  MuHan Lü  3 ,  Hongjuan Cui  1  2  4
Affiliations
  • 1. State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, China.
  • 2. Cancer Center, Medical Research Institute, Southwest University, Chongqing 400716, China.
  • 3. Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan 646000, China.
  • 4. Jinfeng Laboratory, Chongqing 401329, China.
PMID: 37554218 DOI: 10.1016/j.gendis.2023.02.006
Abstract

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.

Keywords
Gastric cancer; PRMT1; Transcriptional regulation; Ubiquitination; β-catenin signaling pathway.
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