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Published on: October 28, 2021
KMT5A Knockdown Suppresses Osteosarcoma Cell Proliferation and Metastasis Through Ꞵ-Catenin Signalling
Jiangdong An1, Jin Zhang2, Zhaoheng Wang1
1Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, P.R. China. email@email.com.
Purpose:
Osteosarcoma (OS) is the most common malignant solid bone tumor in children and young adults. We aimed to investigate the effects and cellular mechanisms of KMT5A on OS cell activity.
Methods:
The protein expression was evaluated in the clinical normal, adjacent and OS osteogenic tissues. Knockdown of KMT5A was achieved by KMT5A siRNAs in a human OS cell line, MG63, to detect cell proliferation and metastasis.
Results:
KMT5A expression was upregulated in clinical OS tissues. Knockdown of KMT5A inhibited cell proliferation but enhanced cell death, with significantly reduced cyclinD1 and Bcl2 and increased cleaved-caspase9 levels. KMT5A knockdown also suppressed OS cell migration and invasion capacity and deceased MMP3 and vimentin expression. β-catenin levels were upregulated in OS tissues and blocking KMT5A resulted in a significant decline in β-catenin expression in the OS cells. Further administration of β-catenin activator remarkably increased protein levels of KMT5A, cyclinD1, Bcl2, MMP3, and vimentin, which showed reversed effects of KMT5A knockdown on OS cell activity.
Conclusion:
KMT5A knockdown plays an inhibitory role in OS cell proliferation and metastasis through β-catenin signalling, which provides basic evidence and suggests potential targets for OS therapeutic research.
Insights
KMT5A knockdown inhibits osteosarcoma (OS) cell proliferation and metastasis. This occurs via the β-catenin signaling pathway, suggesting KMT5A as a potential therapeutic target for OS.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Osteosarcoma (OS) is a prevalent bone cancer in young individuals.
- Understanding the molecular mechanisms driving OS progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role and cellular mechanisms of KMT5A in osteosarcoma.
- To explore KMT5A's impact on OS cell proliferation, metastasis, and survival.
Main Methods:
- KMT5A protein expression was analyzed in clinical osteosarcoma tissues.
- KMT5A was knocked down using siRNAs in the human OS cell line MG63.
- Cell proliferation, death, migration, and invasion assays were performed.
Main Results:
- KMT5A expression is elevated in osteosarcoma tissues.
- KMT5A knockdown reduced proliferation, increased cell death, and suppressed migration/invasion.
- KMT5A knockdown decreased cyclinD1, Bcl2, MMP3, and vimentin, while increasing cleaved-caspase9.
- KMT5A regulates β-catenin signaling, which is upregulated in OS.
Conclusions:
- KMT5A knockdown inhibits osteosarcoma cell proliferation and metastasis.
- The inhibitory effects are mediated through the β-catenin signaling pathway.
- KMT5A represents a potential therapeutic target for osteosarcoma treatment.
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