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

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

机构地区：[1]State Key Laboratory of Silkworm Genome Biology,Southwest University,Chongqing 400716,China [2]Department of Gastroenterology,The Affiliated Hospital of Southwest Medical University,25 Taiping Street,Jiangyang District,Luzhou,Sichuan 646000,China [3]Cancer Center,Medical Research Institute,Southwest University,Chongqing 400716,China [4]Jinfeng Laboratory,Chongqing 401329,China

出　　处：《Genes & Diseases》2023年第6期2622-2638,共17页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82203339);the Postdoctoral Research Foundation of China(No.2021M692679);the Chongqing Postdoctoral Science Foundation(China)(No.7820100607);the Natural Science Foundation Project of Chongqing(China)(No.cstc2021jcyj-bsh0067 and cstc2022ycjh-bgzxm0145).

摘　　要：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 ofβ-catenin,which inducedβ-catenin transcription and activated theβ-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 theβ-catenin signaling pathway.

关 键 词：β-catenin signaling pathway Gastric cancer PRMT1 Transcriptional regulation UBIQUITINATION 

分 类 号：R73[医药卫生—肿瘤]