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

Cancer Communications

article

Jing Han¹  Menglin Nie²  Cong Chen¹  Xiaojing Cheng¹  Ting Guo¹  Longtao Huangfu¹  Xiaomei Li¹  Hong Du¹  Xiaofang Xing¹  Jiafu Ji¹ 

[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;Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University;Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research ,(Ministry of Education), Peking University Cancer Hospital, Beijing Institute for Cancer Research

关键词: SDCBP2-AS1;    gastric cancer;    hnRNP K;    β-catenin;    post-transcriptional modifications;    tumorigenesis;   

DOI  :  10.1002/cac2.12367

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 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 predictive 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 and β-catenin, thereby promoting the degradation of β-catenin in the cytoplasm. Silencing of SDCBP2-AS1 caused SUMOylation of hnRNP K and stabilized β-catenin activity, which altered transcription 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 destabilize β-catenin. These findings suggest SDCBP2-AS1 as a potential target for the treatment of GC.

【 授权许可】

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