Open AccessSDCBP‐AS1 destabilizes β‐catenin by regulating ubiquitination and SUMOylation of hnRNP K to suppress gastric tumorigenicity and metastasis
Author(s) -
Han Jing,
Nie Menglin,
Chen Cong,
Cheng Xiaojing,
Guo Ting,
Huangfu Longtao,
Li Xiaomei,
Du Hong,
Xing Xiaofang,
Ji Jiafu
Publication year - 2022
Publication title -
cancer communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.119
H-Index - 53
ISSN - 2523-3548
DOI - 10.1002/cac2.12367
Subject(s) - sumo protein , ubiquitin , catenin , metastasis , cancer research , ubiquitin ligase , deubiquitinating enzyme , chemistry , biology , cancer , microbiology and biotechnology , genetics , signal transduction , gene , wnt signaling pathway
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.