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

doi:10.1016/j.gendis.2023.02.006

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. eCollection 2023 Nov.

Authors

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 Lü³, 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.

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.