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Published on: March 30, 2019
Integrative analysis in oral squamous cell carcinoma reveals DNA copy number-associated miRNAs dysregulating target
Nicholas A Serrano1, Chang Xu, Yan Liu
1Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98115-7744, USA.
Objective:
To better understand possible mechanisms involved in the dysregulation of gene expression unique to oral squamous cell carcinoma (OSCC) metastasis, the investigators examined the differential expression of microRNAs (miRNAs) in OSCC metastasis and their functional impact on target gene expression.
Study Design:
Observational assessment of DNA copy number, miRNA, and RNA expression in primary and metastatic OSCC.
Setting:
University of Washington Medical Center and affiliated hospitals.
Subjects:
Tumor samples were taken from patients with primary incident OSCC; cells were laser-capture microdissected from 17 nonmetastatic primary tumors and 20 metastatic lymph nodes.
Methods:
DNA copy number aberrations and gene expression profiles were previously determined using Affymetrix 250K Nsp I SNP arrays and HU133 plus 2.0 expression arrays. miRNAs were interrogated with Exiqon's Ready-to-Use PCR Panels assessing the expression of 368 human miRNAs.
Results:
Investigators found 31 miRNAs differentially expressed between metastatic and nonmetastatic samples (false discovery rate <0.4; 26 overexpressed and 5 underexpressed in metastatic samples). Expression of 7 of these miRNAs was significantly associated with their DNA copy numbers, and expressions of 8 of these miRNAs were significantly associated with their target genes. Among these unique miRNAs, miR-140-3p, miR-29c, and miR-29a were differentially expressed in metastasis versus nonmetastatic samples and had a strong positive correlation with their DNA copy numbers and a negative correlation with the expression of their target genes.
Conclusion:
Results suggest that DNA copy number aberration may play a role in the dysregulation of some differentially expressed miRNAs in OSCC metastasis, warranting further investigation.
Insights
Researchers identified 31 microRNAs (miRNAs) with altered expression in oral squamous cell carcinoma (OSCC) metastasis. DNA copy number changes may influence these miRNA dysregulations, impacting gene expression in metastatic OSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Oral squamous cell carcinoma (OSCC) metastasis involves complex gene expression dysregulation.
- MicroRNAs (miRNAs) are key regulators of gene expression and are implicated in cancer progression.
- Understanding miRNA involvement in OSCC metastasis is crucial for identifying therapeutic targets.
Purpose of the Study:
- To investigate the differential expression of miRNAs in OSCC metastasis.
- To explore the functional impact of these differentially expressed miRNAs on target gene expression.
- To elucidate the mechanisms underlying miRNA dysregulation in OSCC metastasis.
Main Methods:
- Observational study assessing DNA copy number, miRNA, and RNA expression in primary and metastatic OSCC.
- Laser-capture microdissection of tumor cells from nonmetastatic primary tumors and metastatic lymph nodes.
- Analysis using SNP arrays, gene expression arrays, and miRNA-specific PCR panels.
Main Results:
- Identified 31 differentially expressed miRNAs between metastatic and nonmetastatic OSCC samples.
- Found significant associations between miRNA expression and DNA copy numbers for 7 miRNAs.
- Observed significant associations between miRNA expression and their target genes for 8 miRNAs, with miR-140-3p, miR-29c, and miR-29a showing strong correlations.
Conclusions:
- DNA copy number aberrations may contribute to the dysregulation of specific miRNAs in OSCC metastasis.
- These findings highlight the potential role of miRNA alterations in OSCC metastatic processes.
- Further research is warranted to fully understand the implications of these miRNA changes.
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