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A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
miR-761 inhibits human osteosarcoma progression by targeting CXCR1
Shaoyun Wang1, Jinyu Zhang2, Guoping Chen2
1Department of Orthopaedics, The First Affiliated Hospital of Kunming Medical University Kunming, P. R. China.
Abstract:
microRNAs (miRs) are endogenous noncoding RNAs that participate in a variety of cellular processes by regulating multiple targets to promote or inhibit cell behaviors. Emerging evidence suggests that miR-761 plays important roles in human cancers to function as either a tumor suppressor gene or an oncogene. However, its biological role in osteosarcoma (OS) remains largely elusive. This study found the expression of miR-761 was significantly reduced in OS tissues and cell lines. CXC receptor-1 (CXCR1), an oncogene which was overexpressed in a variety of human cancers including OS, was identified as a novel target of miR-761 using bioinformatic, luciferase reporter, and western blot analyses. Cell function assays revealed that miR-761 could inhibit cell proliferation and invasion at least partially through targeting CXCR1. Collectively, our present study suggested that miR-761 may be a promising treatment biomarker for OS.
Insights
microRNA-761 (miR-761) is reduced in osteosarcoma (OS) and targets the oncogene CXCR1. Restoring miR-761 inhibits OS cell proliferation and invasion, suggesting its potential as a therapeutic biomarker.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- microRNAs (miRs) are key regulators of cellular processes.
- miR-761's role in human cancers is varied, but its function in osteosarcoma (OS) is unclear.
- CXC receptor-1 (CXCR1) is an oncogene overexpressed in OS.
Purpose of the Study:
- To investigate the biological role and mechanism of miR-761 in osteosarcoma.
- To identify miR-761 targets in OS cells.
- To evaluate miR-761's potential as a diagnostic or therapeutic biomarker for OS.
Main Methods:
- Quantitative real-time PCR to measure miR-761 expression in OS tissues and cell lines.
- Bioinformatic analysis, luciferase reporter assays, and Western blot to validate CXCR1 as a direct target of miR-761.
- Cell proliferation and invasion assays to assess the functional impact of miR-761 in OS.
Main Results:
- miR-761 expression was significantly downregulated in osteosarcoma tissues and cell lines compared to normal controls.
- CXC receptor-1 (CXCR1) was identified as a direct and novel target of miR-761.
- Overexpression of miR-761 suppressed osteosarcoma cell proliferation and invasion, partially via targeting CXCR1.
Conclusions:
- miR-761 functions as a tumor suppressor in osteosarcoma.
- The miR-761/CXCR1 axis plays a critical role in osteosarcoma progression.
- miR-761 represents a potential therapeutic biomarker for osteosarcoma treatment.
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