GATA6-AS1 via Sponging miR-543 to Regulate PTEN/AKT Signaling Axis Suppresses Cell Proliferation and Migration in Gastric Cancer

Mediators Inflamm. 2023 May 26:2023:9340499. doi: 10.1155/2023/9340499. eCollection 2023.

Abstract

Gastric cancer (GC) is one of the most common and lethal cancers worldwide. In view of the prominent roles of long noncoding RNAs (lncRNAs) in cancers, we investigated the specific role and underlying mechanism of GATA binding protein 6 antisense RNA 1 (GATA6-AS1) in GC. Quantitative real-time polymerase chain reaction (qRT-PCR) detected GATA6-AS1 expression in GC cell lines. Functional assays were conducted to explore the role of GATA6-AS1 in GC. Furthermore, mechanism investigations were implemented to uncover the interaction among GATA6-AS1, microRNA-543 (miR-543), and phosphatase and tensin homolog (PTEN). In the present study, it was found that GATA6-AS1 expression is significantly downregulated in GC cell lines. Functionally, GATA6-AS1 markedly suppresses GC cell growth and migration in vitro and in vivo tumorigenesis. Besides tumor suppressor, GATA6-AS1 serves as a miR-543 sponge. Specifically speaking, GATA6-AS1 acts as a competing endogenous RNA (ceRNA) of miR-543 to upregulate the expression of PTEN, thus inactivating AKT signaling pathway to inhibit GC progression. In conclusion, this study has manifested that GATA6-AS1 inhibits GC cell proliferation and migration as a sponge of miR-543 by regulating PTEN/AKT signaling axis, offering new perspective into developing novel GC therapies.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic
  • GATA6 Transcription Factor / genetics
  • GATA6 Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Signal Transduction / genetics
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • RNA, Long Noncoding
  • PTEN protein, human
  • PTEN Phosphohydrolase
  • GATA6 protein, human
  • GATA6 Transcription Factor
  • MIRN543 microRNA, human