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Full Length Article | Open Access

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

Feng Wanga,cShitong Chena,cShihan Penga,cXujun Zhoua,cHouyi Tanga,cHanghua Lianga,cXi Zhonga,cHe Yanga,cXiaoxue Kea,c( )MuHan Lüb( )Hongjuan Cuia,c,d,( )
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716, China
Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, 25 Taiping Street, Jiangyang District, Luzhou, Sichuan 646000, China
Cancer Center, Medical Research Institute, Southwest University, Chongqing 400716, China
Jinfeng Laboratory, Chongqing 401329, China

Peer review under responsibility of Chongqing Medical University.

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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.

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Genes & Diseases
Pages 2622-2638
Cite this article:
Wang F, Chen S, Peng S, et al. PRMT1 promotes the proliferation and metastasis of gastric cancer cells by recruiting MLXIP for the transcriptional activation of the β-catenin pathway. Genes & Diseases, 2023, 10(6): 2622-2638. https://doi.org/10.1016/j.gendis.2023.02.006

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Received: 23 June 2022
Accepted: 03 February 2023
Published: 28 March 2023
© 2023 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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