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Updated: Mar 12, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Deregulated WWOX is involved in a negative feedback loop with microRNA-214-3p in osteosarcoma
Kaituo Gao1, Jijuan Yin1, Jian Dong1
1Department of Orthopedics, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
Abstract:
WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human osteosarcoma, and the restoration of its expression can suppress tumorigenicity in WWOX-negative OS cells. However, its regulatory mechanisms remain to be fully elucidated. In the present study, we demonstrate that WWOX is downregulated and that it regulates proliferation and epithelial-to-mesenchymal transition (EMT)-associated protein expression in osteosarcoma. As shown by our results, WWOX overexpression by transfection with WWOX overexpression plasmids suppressed the proliferation, migration and invasion of osteosarcoma MG63 cells (as shown by MTT and migration and invasion assays). The silencing of microRNA (miR)‑214‑3p by transfection with anti-miR‑14‑3p upregulated WWOX protein expression and also inhibited the proliferation, migration and invasion of osteosarcoma cells. Additionally, we found that WWOX negatively regulated miR‑214‑3p and miR‑10b expression. Our findings define a negative feedback pathway in control of WWOX and miR‑214‑3p expression, thus providing novel molecular targets for the treatment of osteosarcoma.
Insights
WW domain-containing oxidoreductase (WWOX) is downregulated in osteosarcoma, suppressing proliferation and metastasis. Restoring WWOX or inhibiting miR-214-3p offers potential therapeutic strategies for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human osteosarcoma.
- WWOX expression restoration can suppress tumorigenicity in WWOX-negative osteosarcoma (OS) cells.
- Regulatory mechanisms of WWOX in OS require further elucidation.
Purpose of the Study:
- To investigate the role of WWOX in osteosarcoma proliferation and epithelial-to-mesenchymal transition (EMT).
- To identify regulatory pathways involving WWOX and microRNAs in osteosarcoma.
- To explore potential therapeutic targets for osteosarcoma.
Main Methods:
- WWOX overexpression and silencing using transfection with plasmids and anti-miRNA.
- Assessment of cell proliferation, migration, and invasion using MTT and migration/invasion assays.
- Analysis of WWOX, miR-214-3p, and miR-10b expression levels.
Main Results:
- WWOX overexpression suppressed proliferation, migration, and invasion of osteosarcoma MG63 cells.
- Silencing miR-214-3p upregulated WWOX and inhibited osteosarcoma cell proliferation, migration, and invasion.
- WWOX was found to negatively regulate miR-214-3p and miR-10b expression.
Conclusions:
- A negative feedback pathway exists between WWOX and miR-214-3p in osteosarcoma.
- WWOX plays a crucial role in regulating osteosarcoma cell behavior.
- WWOX and miR-214-3p represent potential molecular targets for osteosarcoma therapy.
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