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

Cancer Commun (Lond). 2022 Nov;42(11):1141-1161. doi: 10.1002/cac2.12367. Epub 2022 Oct 9.


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.

Keywords: SDCBP2-AS1; gastric cancer; hnRNP K; post-transcriptional modifications; tumorigenesis; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein K / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein K / metabolism
  • Humans
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Stomach Neoplasms* / pathology
  • Sumoylation / genetics
  • Syntenins / genetics
  • Syntenins / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • RNA, Long Noncoding
  • beta Catenin
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • SDCBP protein, human
  • Syntenins