Abstract 4159: Expression of miRNAs associated with DNA repair capacity in women with breast cancer.

Abstract

Abstract MicroRNAs (miRNA) are endogenous, short (19-24 nucleotides) non-protein-coding RNAs that regulate gene expression at the post-transcriptional level via binding to 3′-untranslated regions of protein-coding transcripts. A low DNA repair capacity (DRC) is an important risk factor for breast cancer (BC). We are currently investigating whether miRNAs expression is associated with dysregulation of DRC in women with BC. To that effect, we obtained plasma from 30 BC cases and 30 controls selected based on their DRC levels. DRC was measured in lymphocytes using a host cell reactivation assay. Samples were analyzed for miRNA expression utilizing protocols from Applied Biosystems (Life Technologies). After QA/QC, 27 BC cases and 29 controls whose DRC data was available from our cohort study were selected and miRNAs isolated from plasma. The miRNA expression profiling was performed utilizing the RT-PCR TaqMan Array Human MicroRNA A Cards v 2.0 (Applied Biosystems). Single-stranded cDNA was synthesized from 200 ng of total RNA in 8 Multiplex RT primer pool reactions containing stem-looped RT primers that were specific to mature miRNAs. U6 snRNA-001973 was selected for normalization based on our own experimental validations. To quantify the association of the miRNA expression the fold change () was estimated for every detector with the p-values based on the t-test. Significant candidate miRNAs were determined with the false discovery rate of 4%. The results showed that twelve miRNAs are underexpressed in patients with BC relative to controls. These candidate miRNAs were associated with the expression of twenty seven DNA repair genes. Two of these genes (RPA3, MMS19L) are part of the NER pathway which has recently been linked to breast carcinogenesis. Our pilot study data suggests that differential expression of some miRNAs might be associated with dysregulation of DRC in women with BC. Supported by grants S06 GM008239-20, MBRS-RISE GM082406 [NIH-NIGMS] and 1SCA157250-2 from the NCI Center to Reduce Health Disparities, and NIH-MBRS Program (NIGMS). Citation Format: Jaime L. Matta, Luisa Morales, Carmen Ortiz, Celestino Zayas, Erick Suarez. Expression of miRNAs associated with DNA repair capacity in women with breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4159. doi:10.1158/1538-7445.AM2013-4159