GABPB1-AS1 Promotes the Development of Osteosarcoma by Targeting SP1 and Activating the Wnt/β-Catenin Pathway

Jingyang Chen1, Meiru Bian2,3, Lingxiao Pan1

  • 1Department of Orthopedics, Ningbo Medical Center Lihuili Hospital, Ningbo 315400, China.

Journal of Oncology
|March 28, 2022
PubMed

Insights

Long non-coding RNA GABPB1-AS1 promotes osteosarcoma (OS) growth by activating the SP1/Wnt/β-catenin pathway and inhibiting miR-199a-3p. Silencing GABPB1-AS1 reduces OS cell proliferation and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma (OS) is a primary bone malignancy with limited treatment options.
  • The role of long non-coding RNAs (lncRNAs) in OS pathogenesis is increasingly recognized.
  • GABPB1-AS1 has been implicated in various cancers, but its specific function in OS requires elucidation.

Purpose of the Study:

  • To investigate the role of GABPB1-AS1 in osteosarcoma (OS) progression.
  • To explore the underlying molecular mechanisms, including interactions with miR-199a-3p and the SP1/Wnt/β-catenin signaling pathway.

Main Methods:

  • GABPB1-AS1 expression was analyzed in OS cell lines (U2OS, HOS, MG63) and a normal cell line (hFOB1.19).
  • GABPB1-AS1 was silenced using siRNA in U2OS and HOS cells.
  • Cell proliferation, clonal formation, and migration were assessed using CCK-8, plate cloning, and Transwell assays.
  • Protein levels of SP1, Wnt, β-catenin, c-Myc, and SOX2 were analyzed via Western blot.
  • The interaction between GABPB1-AS1 and miR-199a-3p was confirmed using a dual-luciferase reporter assay.

Main Results:

  • GABPB1-AS1 expression was significantly upregulated in OS cell lines compared to hFOB1.19.
  • Silencing GABPB1-AS1 markedly inhibited proliferation, clonal formation, migration, and epithelial-mesenchymal transition in OS cells.
  • A direct binding relationship between GABPB1-AS1 and miR-199a-3p was established.
  • GABPB1-AS1 was found to upregulate SP1, Wnt, β-catenin, c-Myc, and SOX2, indicating activation of the SP1/Wnt/β-catenin pathway.

Conclusions:

  • GABPB1-AS1 acts as a carcinogenic factor in osteosarcoma.
  • GABPB1-AS1 promotes OS progression by competitively binding and inhibiting miR-199a-3p, thereby activating the SP1/Wnt/β-catenin signaling pathway.
  • GABPB1-AS1 represents a potential therapeutic target for osteosarcoma treatment.

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