Long non-coding RNA BC002811 Promotes Gastric Cancer Metastasis by Regulating SOX2 Binding to the PTEN Promoter

Int J Biol Sci. 2023 Jan 16;19(3):967-980. doi: 10.7150/ijbs.76407. eCollection 2023.

Abstract

There is increasing evidence that long non-coding RNAs (lncRNAs) are involved in the pathogenesis and progression of gastric cancer (GC), however, the underlying mechanisms remain poorly understood. In this study, we identified lncRNA BC002811 as a critical regulator of GC development and progression. BC002811 was upregulated in GC tissues and cell lines, and that high expression of BC002811 was indicative of a reduction in overall survival of GC patients. Our research reveals that BC002811 promoted GC cell proliferation, migration, invasion, and inhibition of apoptosis in vitro, as well as accelerated tumor growth and metastasis in vivo. We also found that BC002811 upregulated MMP2 and MMP9 and promoted GC cell metastasis partially through downregulating PTEN expression. BC002811 may act as a molecular decoy for the transcription factor SOX2, thereby inhibiting the transcription of PTEN by blocking SOX2 binding to the PTEN promoter. Our study advances the understanding of the role of BC002811 in the pathogenesis of GC and provides new molecular targets for therapeutic intervention against GC metastasis.

Keywords: Gastric cancer; Long non-coding RNA; PTEN; Tumor metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • RNA, Long Noncoding* / genetics
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Stomach Neoplasms* / metabolism

Substances

  • RNA, Long Noncoding
  • PTEN protein, human
  • PTEN Phosphohydrolase
  • SOX2 protein, human
  • SOXB1 Transcription Factors