Association of DNA Copy Number and miRNA Expression in OSCC

Objective: Better understand possible mechanisms involved in the dysregulation unique to OSCC metastasis, we examined whether DNA copy number aberrations (CNAs) are associated with differential expression of miRNA that are found in OSCC metastasis. Method: Tumor cells were laser capture microdissected from 17 nonmetastatic primary tumors and 20 metastatic lymph nodes. CNAs and gene expression profiles were previously determined using Affymetrix 250K Nsp I SNP Arrays and HU133 plus 2.0 expression profiles. MiRNAs were interrogated with Exiqon’s Ready-to-use PCR Panels. Results: We found 155 miRNAs expressed in >80% of metastatic or nonmetastatic samples with 31 of them differentially expressed in metastatic tumor cells (FDR<0.4; 27 over-expressed, 4 under-expressed). We found the expression of 11 miRNAs to be significantly associated with their DNA copy numbers (p < 0.5) and 7 of these were among the differentially expressed miRNAs. Among these, miR-140-3p, miR-29c, and miR-29a showed a correlation between their expression and corresponding DNA copy number. These miRNAs were also associated with the down-regulation of their target genes in the MAP/ERK oncogenic pathway. Conclusion: Our results suggest that DNA copy number aberration may play a role in the dysregulation of miRNA in OSCC metastasis and that copy number driven miRNAs warrant further investigation.