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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
MicroRNA‑376a inhibits cell proliferation and invasion in osteosarcoma via directly targeting SATB1
Guanghong Zhou1, Hao Jiang1, Liping Ma2
1Department of Surgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Abstract:
Aberrantly expressed microRNAs (miRs) are implicated in the regulation of osteosarcoma (OS) onset and development. Therefore, key miRs in OS must be identified to develop promising and effective therapeutic targets for patients with OS. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis revealed that miR‑376a‑3p expression was downregulated in OS tissues and cell lines. Additionally, decreased miR‑376a expression was associated with tumor size and lymph node infiltration. Restoration of miR‑376a expression reduced cell proliferation and invasion of OS. Furthermore, special AT‑rich sequence‑binding protein 1 (SATB1) was identified as a direct target gene of miR‑376a in OS cells. Furthermore, SATB1 was overexpressed in OS tissues and SATB1 overexpression was inversely correlated with the expression level of miR‑376a. In addition, ectopic SATB1 expression counteracted the inhibitory effects of miR‑376a overexpression on the proliferation and invasion of OS cells. All these results identified that reduced miR‑376a expression may be implicated in the mechanism underlying OS progression, suggesting that the miR‑376a/SATB1 axis may be a promising novel target for potential therapeutic methods for the effective treatment of patients with OS.
Insights
microRNAs (miRs) regulate osteosarcoma (OS) development. Reduced miR-376a-3p expression in OS promotes tumor growth and invasion by upregulating SATB1, suggesting a new therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant microRNA (miR) expression is crucial in osteosarcoma (OS) pathogenesis.
- Identifying key miRs is essential for developing effective OS therapies.
Purpose of the Study:
- To investigate the role of miR-376a-3p in osteosarcoma.
- To identify the molecular mechanisms underlying miR-376a-3p's function in OS.
Main Methods:
- Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to assess miR-376a-3p expression.
- Cell proliferation and invasion assays.
- Bioinformatic analysis and Western blotting to identify miR-376a-3p targets.
Main Results:
- miR-376a-3p was significantly downregulated in OS tissues and cell lines.
- Lower miR-376a-3p expression correlated with larger tumor size and lymph node metastasis.
- Restoring miR-376a-3p suppressed OS cell proliferation and invasion.
- SATB1 was identified as a direct target of miR-376a-3p and was overexpressed in OS.
- SATB1 overexpression reversed the inhibitory effects of miR-376a-3p.
Conclusions:
- Reduced miR-376a-3p expression contributes to OS progression.
- The miR-376a-3p/SATB1 axis represents a potential therapeutic target for osteosarcoma treatment.
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