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 hair...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.展开更多
基金supported by the National Natural Science Foundation of China(No.82203339)the Postdoctoral Research Foundation of China(No.2021M692679)+1 种基金the Chongqing Postdoctoral Science Foundation(China)(No.7820100607)the Natural Science Foundation Project of Chongqing(China)(No.cstc2021jcyj-bsh0067 and cstc2022ycjh-bgzxm0145).
文摘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.
