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Published on: May 3, 2021
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.
Abstract:
In this study, the role of GABPB1-AS1 in osteosarcoma (OS) was analyzed. The expression of GABPB1-AS1 in different OS cell lines U2OS, HOS, MG63, and hFOB1.19 was detected. SiRNA GABPB1-AS1 was transfected with U2OS and HOS cell lines. The effects of GABPB1-AS1 silencing on proliferation, clonal formation, and migration of U2OS and HOS were detected by CCK-8 method, plate cloning method, and Transwell chamber. Western blot analysis was used to detect the protein levels of SP1, Wnt, β-catenin, c-Myc, and SOX2 in osteosarcoma cells. The binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells was detected by a dual-luciferase reporter gene assay. Results showed that GABPB1-AS1 was higher in OS cells than that in hFOB1.19. Silencing GABPB1-AS1 inhibited the proliferation, clonal formation, migration, and epithelial-mesenchymal transformation of U2OS and HOS. There was a binding relationship between GABPB1-AS1 and miR-199a-3p in OS cells. GABPB1-AS1 mediated osteosarcoma cells via the SP1/Wnt/β-catenin signaling pathway. This study suggested that GABPB1-AS1 plays a carcinogenic role in OS through the SP1/Wnt/β-catenin signaling pathway through competitive binding and inhibition of miR-199a-3p.
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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