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Updated: Jan 23, 2026

Author Spotlight: RNA FISH for Locating lncRNA-SNHG6 in Osteosarcoma Cells
Published on: June 16, 2023
HIF-1α induced long noncoding RNA FOXD2-AS1 promotes the osteosarcoma through repressing p21
Zhipeng Ren1, Yongcheng Hu2, Guishi Li3
1Department of Orthopaedics, Tianjin Hospital, Tianjin, 300211, China; Graduate School, Tianjin Medical University, Tianjin, 300070, China.
Abstract:
Emerging literature indicates the essential roles of long noncoding RNA (lncRNA) in the osteosarcoma (OS). However, the regulatory function and mechanism of FOXD2-AS1 in the OS is still elusive. In present research, the level of FOXD2-AS1 was significantly up-regulated in the OS tissue and cell lines compared to corresponding controls. The aberrant high-expression of FOXD2-AS1 indicated the poor clinical prognosis of OS patients. Transcription factor HIF-1α could bind with the promoter region of FOXD2-AS1 to activate the transcription in OS cells. Functionally, the knockdown of FOXD2-AS1 could repress the malignant biological properties of OS cells in vitro and vivo, including proliferation, invasion, apoptosis and tumor growth. Mechanistically, FOXD2-AS1 inhibited the expression of p21 via interacting with EZH2 to silence p21 gene expression. Overall, we conclude that FOXD2-AS1, induced by transcription factor HIF-1α, acts as an oncogene in the OS tumorigenesis and FOXD2-AS1 interacts with EZH2 to silence p21 protein. This finding could provide a novel insight and potential therapeutic target for the OS.
Insights
FOXD2-AS1 is highly expressed in osteosarcoma (OS) and promotes tumor growth by inhibiting p21. This long noncoding RNA, regulated by HIF-1α, represents a potential therapeutic target for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) play crucial roles in osteosarcoma (OS) development.
- The specific regulatory function of FOXD2-AS1 in OS remains unclear.
Purpose of the Study:
- To investigate the role and mechanism of FOXD2-AS1 in osteosarcoma.
- To explore FOXD2-AS1 as a potential therapeutic target for OS.
Main Methods:
- Quantitative real-time PCR to measure FOXD2-AS1 expression in OS tissues and cell lines.
- Analysis of the correlation between FOXD2-AS1 expression and clinical prognosis.
- Investigation of HIF-1α binding to the FOXD2-AS1 promoter.
- In vitro and in vivo experiments to assess the functional impact of FOXD2-AS1 knockdown.
- Western blot and co-immunoprecipitation assays to elucidate the interaction between FOXD2-AS1, EZH2, and p21.
Main Results:
- FOXD2-AS1 expression was significantly upregulated in OS tissues and cell lines, correlating with poor prognosis.
- Transcription factor HIF-1α activates FOXD2-AS1 transcription in OS cells.
- Knockdown of FOXD2-AS1 suppressed OS cell proliferation, invasion, and tumor growth in vitro and in vivo.
- FOXD2-AS1 interacts with EZH2 to epigenetically silence p21 expression, inhibiting tumor suppressor activity.
Conclusions:
- FOXD2-AS1 acts as an oncogene in osteosarcoma tumorigenesis, induced by HIF-1α.
- FOXD2-AS1 promotes OS progression by interacting with EZH2 to repress p21.
- Targeting FOXD2-AS1 may offer a novel therapeutic strategy for osteosarcoma.
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