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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
MicroRNA‑302a suppresses cell proliferation, migration and invasion in osteosarcoma by targeting ADAM9
Xiaoming Yang1, Yan Cui1, Fuqiang Yang1
1Department of Orthopedics, 89th Hospital of PLA, Weifang, Shandong 261021, P.R. China.
Abstract:
Osteosarcoma (OS) is the most frequent malignant primary bone tumor arising from primitive bone‑forming mesenchymal cells in children and adolescents. The dysregulation of microRNAs (miRNAs) has been reported in OS, and these aberrantly expressed miRNAs are involved in the initiation and progression of OS. The aim of the present study was to investigate the expression and functions of miRNA‑302a (miR‑302a) in OS and its underlying mechanism. It was found that the expression of miR‑302a was reduced in OS tissues and cell lines. The low expression of miR‑302a was significantly correlated with tumor‑node‑metastasis stage and metastasis. The ectopic overexpression of miR‑302a inhibited the proliferation, migration and invasion of OS cells. Bioinformatics analysis showed that a disintegrin and metalloproteinase 9 (ADAM9) was a potential target gene of miR‑302a. Subsequently, reverse transcription‑quantitative polymerase chain reaction and western blot analyses revealed that miR‑302a regulated the expression of ADAM9 at the post‑transcriptional level in OS cells. In addition, a luciferase reporter assay demonstrated that miR‑302a directly targeted the 3'untranslated region of ADAM9. In clinical OS tissues, the mRNA expression of ADAM9 was upregulated and inversely correlated with the expression of miR‑302a. In addition, the effects of ADAM9 knockdown on cell proliferation, migration and invasion were similar to those induced by the overexpression of miR‑302a in OS cells. These findings suggested that miR‑302a inhibited OS cell growth and metastasis by targeting ADAM9. miR‑302a may serve as a potential therapeutic target for patients with OS.
Insights
MicroRNA-302a (miR-302a) is reduced in osteosarcoma (OS), inhibiting tumor growth and metastasis by targeting ADAM9. This finding suggests miR-302a as a potential therapeutic target for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a primary bone cancer in children and adolescents.
- MicroRNA (miRNA) dysregulation is implicated in OS initiation and progression.
Purpose of the Study:
- Investigate the expression and function of microRNA-302a (miR-302a) in osteosarcoma.
- Elucidate the underlying molecular mechanism of miR-302a in OS.
Main Methods:
- Quantitative polymerase chain reaction and western blot analyses.
- Bioinformatics analysis and luciferase reporter assays.
- In vitro cell proliferation, migration, and invasion assays.
Main Results:
- miR-302a expression was significantly reduced in OS tissues and cell lines, correlating with advanced tumor stage and metastasis.
- Overexpression of miR-302a suppressed OS cell proliferation, migration, and invasion.
- miR-302a directly targeted and downregulated ADAM9 expression at the post-transcriptional level.
- ADAM9 knockdown mimicked the anti-tumor effects of miR-302a overexpression.
Conclusions:
- miR-302a inhibits osteosarcoma cell growth and metastasis by targeting ADAM9.
- miR-302a represents a potential therapeutic target for osteosarcoma treatment.
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