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Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
Published on: November 5, 2014
Factors Associated with Promoted Proliferation of Osteosarcoma by Peptidylarginine Deiminase 4
Jianping Guo1, Lei Yin2, Xuezhong Zhang3
1Department of Oncology, Maternal and Child Health Care Hospital of Zibo, Zibo 255029, China.
Abstract:
Osteosarcoma is the most common type of bone malignancy, and the pathogenesis has not been entirely elucidated yet. An important deimination modification enzyme PADI4 (peptidylarginine deiminase 4) has attracted much attention in recent years for its important function in several kinds of human tumors. However, the role of PADI4 on osteosarcoma tumorigenesis remains largely unrevealed. Here, we first assessed the effect of PADI4 on osteosarcoma proliferation by the CCK8 method and colony formation assay. Ectopically expressing PADI4 positively regulates the colony formation capacity of both U2OS and Saos-2 cells. Furthermore, we explored the related mechanism and showed that PADI4 could stimulate Wnt/β-catenin and MEK/ERK signaling in both U2OS and Saos-2 cells. Then, we detected expression of PADI4 in human tissues of osteosarcoma and revealed that differential expression of PADI4 was associated with tumorigenesis of osteosarcoma. Last, we performed the in vivo experiment in nude mice and results also showed PADI4 could affect the tumor growth. In conclusion, this work revealed that PADI4 could upregulate the proliferation of osteosarcoma, mainly via the Wnt/β-catenin and MEK/ERK signaling pathway. This study gives us new insight into the regulation mechanism of osteosarcoma proliferation and highlights PADI4 as a promising target for osteosarcoma diagnosis and treatment.
Insights
Peptidylarginine deiminase 4 (PADI4) promotes osteosarcoma proliferation by activating Wnt/β-catenin and MEK/ERK signaling pathways. This finding offers new insights into osteosarcoma development and identifies PADI4 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is the most common primary bone cancer, but its pathogenesis is not fully understood.
- Peptidylarginine deiminase 4 (PADI4), an enzyme involved in deimination, plays a role in various human cancers.
- The specific role of PADI4 in osteosarcoma tumorigenesis requires further investigation.
Purpose of the Study:
- To investigate the effect of PADI4 on osteosarcoma cell proliferation.
- To elucidate the underlying molecular mechanisms by which PADI4 influences osteosarcoma.
- To assess the clinical relevance of PADI4 expression in osteosarcoma tissues and its impact on tumor growth.
Main Methods:
- Cell proliferation was assessed using the CCK8 assay and colony formation assay.
- Signaling pathways, including Wnt/β-catenin and MEK/ERK, were analyzed.
- PADI4 expression was examined in human osteosarcoma tissues.
- In vivo experiments were conducted using nude mice to evaluate tumor growth.
Main Results:
- Ectopic expression of PADI4 enhanced the proliferation and colony formation capacity of osteosarcoma cells (U2OS and Saos-2).
- PADI4 was found to stimulate both the Wnt/β-catenin and MEK/ERK signaling pathways.
- Differential expression of PADI4 correlated with osteosarcoma tumorigenesis.
- In vivo studies confirmed that PADI4 affects tumor growth in osteosarcoma models.
Conclusions:
- PADI4 significantly upregulates osteosarcoma proliferation, primarily through the activation of Wnt/β-catenin and MEK/ERK signaling.
- This study provides novel insights into the regulatory mechanisms of osteosarcoma proliferation.
- PADI4 emerges as a promising biomarker for osteosarcoma diagnosis and a potential therapeutic target for treatment.
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