Abstract 3160: Expression of apoptosis-regulating miRNAs and target mRNAs in oral squamous cell carcinoma

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Apoptosis is a genetically programmed form of cell death, which primarily functions to eliminate senescent or altered cells that are useless or harmful for the multicellular organism. In contrast, aberrations of the apoptotic mechanisms that cause excessive or deficient programmed cell death have been linked to a wide array of pathologic conditions. MicroRNAs (miRNAs) are approximately 22 nucleotide non-coding RNA molecules that regulate gene expression post-transcriptionally and recent studies have indicated the dysregulation of miRNAs involved in apoptosis. In this study, using Real Time RT-PCR we have analyzed the expression of apoptosis-regulating miRNAs (miR-15a, miR-16, miR-29a, miR-34a, miR-17-5p, miR20a, miR21) in a series of 20 oral squamous cell carcinoma samples and a pool of 5 normal oral mucosa tissue samples. Using TargetScan algorithms, target genes of these miRNAs were identified and the expression of mRNA transcripts of these target genes was also evaluated (Bcl-2, Caspase-2, Caspase-7, Bid, SMAC/DIABLO) in a series of 50 oral squamous cell carcinoma samples and a pool of 10 normal oral mucosa tissue samples. Considering up- or down-regulation as a 2-fold difference in expression relative to the normal tissue, we observed down-regulation of miR-15a, miR29a and miR34a in 50%, 75% and 70% of the samples, respectively. Normal-like expression was observed for miR-16, miR-17-5p, miR-20a and miR-21 in 80%, 75%, 90% and 60% of the samples, respectively. Down-regulation of the BCL-2 transcripts was observed in 60% of the samples and normal-like expression was observed for BID, CASPASE-2, CASPASE-7 and SMAC/DIABLO transcripts in 66%, 82%, 68% and 60% of the samples, respectively. Expression of BID, CASPASE-2 and CASPASE-7 might be regulated by miR-17-5p and miR-20a and we found no alteration in expression of both mRNAs and miRNAs. Expression of BCL-2 might be regulated by miR-15a, miR-16, miR-21 and miR-34. We found down-regulation of BCL-2 transcripts and miRNAs-15a and -34, suggesting that other mechanisms might be involved in the regulation of BCL-2. Expression of SMAC/DIABLO might be regulated by miR-29 and we found normal-like expression of SMAC/DIABLO transcripts and down-regulation of miRNA-29 also suggesting that other mechanisms might be involved in the regulation of SMAC/DIABLO. Our study provides evidence of alterations in the expression of apoptosis-regulating miRNAs and alterations in the expression of genes involved in the apoptotic pathway demonstrating that regulation of apoptosis is an important feature in OSCC behavior. FAPESP research grants 98/14335-2 and 07/50608-4. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3160. doi:1538-7445.AM2012-3160