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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
MicroRNA-337-5p participates in the development and progression of osteosarcoma via ERBB, MAPK and VEGF pathways
1Department of Orthopedics, The First People's Hospital of Wujiang District, Suzhou, China. zhuangyan_bmu@126.com.
Objective:
To investigate the role of microRNA-337-5p in osteosarcoma (OS) and its underlying mechanism.
Patients And Methods:
The microRNA (microRNA-337-5p) that may be related to OS development was screened out by GEO (Gene Expression Omnibus) database. Survival analysis and ROC curve were performed according to microRNA-337-5p expressions in OA patients. Besides, the correlation between microRNA-337-5p expression and clinical parameters was evaluated by Chi-square analysis. Cox regression analysis was performed to detect the relationship between the overall survival and clinical parameters of OA patients. Subsequently, enriched functions and pathways of microRNA-337-5p were predicted by GESA (gene enrichment sets analysis). MicroRNA-337-5p expression was detected in 65 OS tissue samples and 30 normal tissue samples by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). For in vitro experiments, after microRNA-337-5p mimics or microRNA-337-5p inhibitor was transfected into OS cells, proliferative and invasive abilities were detected by CCK-8 (Cell Counting Kit-8) and transwell assay, respectively. Finally, Western blot was used to explore the underlying mechanism of microRNA-337-5p in regulating OS.
Results:
MicroRNA-337-5p was overexpressed in serum and tissue samples of OS patients, which was valuable in diagnosing OS. Besides, microRNA-337-5p expression was correlated with the overall survival and necrosis range of OA patients, whereas not correlated with age and sex. GESA indicated that microRNA-337-5p was enriched in ERBB, MAPK, and VEGF pathways. In vitro experiments indicated elevated proliferative and invasive abilities in MG63 and U2OS cells after microRNA-337-5p overexpression. Furthermore, increased expressions of ERBB2, Erk1/2, and VEGF121 were observed in OS cells after microRNA-337-5p overexpression.
Conclusions:
MicroRNA-337-5p is upregulated in OS tissues, which is an independent prognostic factor in OS. Overexpressed microRNA-337-5p can promote proliferative and invasive abilities of OS cells via activating ERBB, MAPK, and VEGF pathways.
Insights
MicroRNA-337-5p is overexpressed in osteosarcoma (OS) and promotes cancer cell growth and invasion. This microRNA is a potential diagnostic marker and therapeutic target for OS patients.
Area of Science:
- Molecular Oncology
- Biomarkers in Cancer
Background:
- Osteosarcoma (OS) is a primary bone malignancy with significant mortality.
- MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
- The specific role of microRNA-337-5p in OS remains to be fully elucidated.
Purpose of the Study:
- To investigate the expression and function of microRNA-337-5p in osteosarcoma.
- To explore the underlying molecular mechanisms by which microRNA-337-5p influences OS progression.
- To evaluate microRNA-337-5p as a potential diagnostic and prognostic biomarker for OS.
Main Methods:
- Screening of potential OS-related miRNAs using the GEO database.
- Survival analysis, ROC curves, and correlation analysis with clinical parameters.
- Gene Enrichment Sets Analysis (GESA) to predict pathways.
- Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) for miRNA expression analysis.
- In vitro cell proliferation (CCK-8) and invasion (Transwell) assays.
- Western blot to investigate protein expression changes.
Main Results:
- MicroRNA-337-5p was significantly overexpressed in OS tissues and serum samples.
- Higher microRNA-337-5p expression correlated with poorer overall survival and larger necrosis range in OS patients.
- GESA revealed enrichment in ERBB, MAPK, and VEGF signaling pathways.
- Overexpression of microRNA-337-5p in OS cells increased proliferation and invasion.
- Increased expression of ERBB2, Erk1/2, and VEGF121 was observed following microRNA-337-5p upregulation.
Conclusions:
- MicroRNA-337-5p is upregulated in osteosarcoma and serves as an independent prognostic factor.
- Overexpressed microRNA-337-5p promotes OS cell proliferation and invasion.
- The oncogenic effects are mediated through the activation of ERBB, MAPK, and VEGF pathways.
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