SDCBP-AS1 destabilizesβ-catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis  

作　　者：Jing Han Menglin Nie Cong Chen Xiaojing Cheng Ting Guo Longtao Huangfu Xiaomei Li Hong Du Xiaofang Xing Jiafu Ji 

机构地区：[1]Department of Gastrointestinal Cancer Translational Research Laboratory,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital,Beijing Institute for Cancer Research,Beijing 100142,P.R.China [2]Department of Radiation Oncology,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,P.R.China [3]Department of Gastrointestinal Surgery,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Peking University Cancer Hospital,Beijing Institute for Cancer Research,Beijing 100142,P.R.China

出　　处：《Cancer Communications》2022年第11期1141-1161,共21页癌症通讯（英文）

基　　金：the National High Technology Research and Development Program of China,Grant/Award Number:2014AA020603;Clinical Medicine Plus X-Young Scholars Project of Peking University,Grant/Award Number:PKU2020LCXQ001;the Joint Fund for the Key Projects of National Natural Science Foundation of China,Grant/Award Number:U20A20371;“Double First Class”disciplinary development Foundation of Peking University,Grant/Award Number:BMU2019LCKXJ011;National Natural Science Foundation of China,Grant/Award Numbers:81802471,81872502,81972758,82103528;Beijing Municipal Medical Research Institutes,Grant/Award Number:2019-1;Beijing municipal administration of hospitals’youth program,Grant/Award Number:QML20181102。

摘　　要：Background:Gastric cancer(GC)is among the most malignant tumors,yet the pathogenesis is not fully understood,especially the lack of detailed information about the mechanisms underlying long non-coding RNA(lncRNA)-mediated post-translational modifications.Here,the molecular mechanisms and clinical significance of the novel lncRNA syndecan-binding protein 2-antisense RNA 1(SDCBP2-AS1)in the tumorigenesis and progression of GC were investigated.Methods:The expression levels of SDCBP2-AS1 in 132 pairs of GC and adjacent normal tissues were compared,and the biological functions were assessed in vitro and in vivo.RNA pull-down and immunoprecipitation assays were conducted to clarify the interactions of SDCBP2-AS1 and heterogeneous nuclear ribonucleoprotein(hnRNP)K.RNA-sequencing,immunoprecipitation,immunofluorescence,and luciferase analyses were performed to investigate the functions of SDCBP2-AS1.Results:SDCBP2-AS1 was significantly downregulated in GC tissues and pre-dictive of poor patient prognosis.Silencing of SDCBP2-AS1 promoted the proliferation and migration of GC cells both in vitro and in vivo.Mechanically,SDCBP2-AS1 physically bound to hnRNP K to repress SUMOylation of hnRNP K and facilitated ubiquitination of hnRNP K andβ-catenin,thereby promoting the degradation ofβ-catenin in the cytoplasm.Silencing of SDCBP2-AS1 caused SUMOylation of hnRNP K and stabilizedβ-catenin activity,which altered tran-scription of downstream genes,resulting in tumorigenesis and metastasis of GC.Moreover,the knockdown of hnRNP K partially abrogated the effects of SDCBP2-AS1.Conclusions:SDCBP2-AS1 interacts with hnRNP K to suppress tumorigenesis and metastasis of GC and regulates post-transcriptional modifications of hnRNP K to destabilizeβ-catenin.These findings suggest SDCBP2-AS1 as a potential target for the treatment of GC.

关 键 词：SDCBP2-AS1 gastric cancer hnRNP K Β-CATENIN post-transcriptional modifications tumori-genesis 

分 类 号：R735.2[医药卫生—肿瘤]