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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
miR-1 Inhibits Cell Growth, Migration, and Invasion by Targeting VEGFA in Osteosarcoma Cells
Junjie Niu1, Yibao Sun2, Qiaoge Guo3
1Department of Radiology, Zhengzhou Orthopedics Hospital, Zhengzhou, China.
Abstract:
microRNAs (miRNAs) are small noncoding RNAs and have been shown to play a crucial role in the osteosarcoma (OS) tumorigenesis and progression. VEGFA is a key regulator of angiogenesis and plays an important role in regulation of tumor metastasis. The objective of this study was to determine whether VEGFA was involved in miR-1-mediated suppression of proliferation, migration, and invasion of OS cells. The expression levels of miR-1 were significantly lower in OS tumor tissues than those in adjacent normal tissues and in SAOS-2 and U2OS cell lines compared to a normal osteoblast (NHOst) cell line. VEGFA was upregulated in OS tumor tissues and SAOS-2 and U2OS cell lines. The results of CCK-8 assay and transwell assay showed that miR-1 acted as a tumor suppressor by inhibiting cell proliferation, migration, and invasion in U2OS cells. Dual luciferase reporter assay demonstrated that VEGFA was a direct and functional target gene of miR-1. miR-1 directly inhibits the protein expression of VEGFA via its 3'-UTR. Knockdown of VEGFA by siRNA inhibited proliferation, migration, and invasion of U2OS cells. Our study suggested the potential inhibitory function of miR-1 in OS cell proliferation, migration, and invasion via inhibiting VEGFA.
Insights
MicroRNAs (miRNAs) act as tumor suppressors in osteosarcoma (OS) by inhibiting cell proliferation and metastasis. This study reveals that miR-1 directly targets VEGFA, suppressing OS progression.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- MicroRNAs (miRNAs) are critical regulators in cancer development, including osteosarcoma (OS).
- Vascular Endothelial Growth Factor A (VEGFA) is implicated in tumor growth and metastasis.
Purpose of the Study:
- To investigate the role of miR-1 in osteosarcoma (OS) progression.
- To determine if VEGFA is a direct target of miR-1 in OS cells.
Main Methods:
- Quantitative real-time PCR to measure miR-1 and VEGFA expression.
- Cell proliferation, migration, and invasion assays (CCK-8, Transwell).
- Dual-luciferase reporter assay to confirm direct targeting of VEGFA by miR-1.
Main Results:
- miR-1 expression was significantly downregulated in OS tissues and cell lines.
- VEGFA expression was upregulated in OS tissues and cell lines.
- miR-1 suppressed OS cell proliferation, migration, and invasion, and directly targeted VEGFA.
- VEGFA knockdown mimicked the tumor-suppressive effects of miR-1.
Conclusions:
- miR-1 functions as a tumor suppressor in osteosarcoma.
- The miR-1/VEGFA axis plays a significant role in inhibiting OS cell proliferation, migration, and invasion.
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