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A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
ACTN4 Promotes the Proliferation, Migration, Metastasis of Osteosarcoma and Enhances its Invasive Ability through the
Qingshan Huang1, Xiaodong Li1, Zhen Huang1
1Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Abstract:
Alpha-actinin-4 (ACTN4) is associated with different types of tumors, but its role in osteosarcoma (OS) is not known. We aimed to investigate the effect of ACTN4 on the growth, migration, invasion and metastasis of OS. We further explored the possible mechanism of how ACTN4 affects the development of OS. First, the expression of ACTN4 in OS tissues and OS cell lines was analyzed by PCR. Second, the role of ACTN4 in the development of OS was explored by the proliferation, scratch, and invasion assays. We further explored the effect of ACTN4 on OS growth in an orthotopic xenograft model of nude mice. In addition, we used hematoxylin and eosin (HE) staining of lung tissues in nude mice to observe the effect of ACTN4 on lung metastasis of OS. Finally, rescue experiments further investigated the role of NF-κB on ACTN4 in the development of OS. ACTN4 was highly expressed in OS tissues and OS cell lines. In vitro experiments demonstrated that reducing ACTN4 expression inhibited the proliferation, migration, and invasion of OS. In contrast, overexpression of ACTN4 promotes these effects. In vivo experiments further validated that ACTN4 promoted the growth of OS. The HE staining of lungs in nude mice revealed that ACTN4 promoted lung metastasis of OS. In addition, we found that ACTN4 enhanced the ability of OS to invade, through the NF-κB pathway. ACTN4 promotes the proliferation, migration, metastasis of OS and enhances its invasion ability through the NF-κB pathway.
Insights
Alpha-actinin-4 (ACTN4) promotes osteosarcoma (OS) growth, migration, and metastasis. This study reveals ACTN4 enhances OS invasion via the NF-κB pathway, identifying a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Alpha-actinin-4 (ACTN4) is implicated in various cancers, but its specific role in osteosarcoma (OS) remains uncharacterized.
- Understanding ACTN4's function in OS is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of ACTN4 in osteosarcoma (OS) progression, including growth, migration, invasion, and metastasis.
- To elucidate the underlying molecular mechanism, specifically the involvement of the NF-κB pathway.
Main Methods:
- Quantitative PCR (qPCR) to analyze ACTN4 expression in OS tissues and cell lines.
- In vitro assays (proliferation, scratch, invasion) to assess ACTN4's functional impact.
- In vivo orthotopic xenograft models and lung metastasis studies in nude mice.
- Rescue experiments to confirm the role of the NF-κB pathway.
Main Results:
- ACTN4 expression was significantly upregulated in OS tissues and cell lines.
- Reduced ACTN4 expression inhibited OS cell proliferation, migration, and invasion in vitro.
- Overexpression of ACTN4 enhanced these malignant phenotypes.
- In vivo studies confirmed ACTN4 promotes OS tumor growth and lung metastasis.
- ACTN4 facilitates OS invasion through activation of the NF-κB pathway.
Conclusions:
- ACTN4 is a key driver of osteosarcoma progression, promoting proliferation, migration, invasion, and metastasis.
- The NF-κB pathway is essential for ACTN4-mediated OS invasion.
- Targeting ACTN4 may represent a novel therapeutic strategy for osteosarcoma.
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