Integrative Analysis in Oral Squamous Cell Carcinoma Reveals DNA Copy Number–Associated miRNAs Dysregulating Target Genes

Abstract

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.