Abstract P5-06-05: miRNAs associated with DNA repair capacity in Puerto Rican women with breast cancer

Abstract

Abstract BACKGROUND: MicroRNAs (miRNA) are short non-protein-coding RNAs that regulate gene expression at the post-transcriptional level via binding to 3′-untranslated regions of protein-coding transcripts. Some miRNAs have been used as diagnostic, prognostic and therapeutic markers of breast cancer (BC). It is well established that dysregulation of DNA repair capacity (DRC) is an important risk factor of BC. However, there is little published information as to what specific miRNAs are associated with DRC in women with BC. OBJECTIVE: The main objective of this study was to identify candidate miRNAs associated with dysregulation of DRC in women with BC. METHODS: Plasma samples from 30 BC cases and 30 controls selected based on their DRC levels (low, high) using a proprietary algorithm. Samples were analyzed for miRNA expression utilizing protocols from Applied Biosystems (Life Technologies). The miRNA expression profiling was performed utilizing the RT-PCR TaqMan Array Human MicroRNA A Cards v 2.0 (Applied Biosystems) containing 383 miRNA probes. 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 calculated using the t-test. RESULTS: Candidate miRNAs that showed a statistically significant expression were: miR-146, miR-34a, miR-221, Let-7b, miR-193b, miR-132, miR-192, miR-21, miR-197, miR-24, miR-26b, miR-29c were identified based on a false discovery rate of 4%. The results showed that twelve miRNAs differentially expressed in patients with BC. Candidate miRNAs have been reported associated with the expression of twenty seven DNA repair genes. Two of these genes are part of the NER pathway which has been identified by previous studies as important in BC. CONCLUSION: Our preliminary data suggests that differential expression of specific miRNAs might be associated with dysregulation of DRC in BC. The molecular mechanisms by which miRNAs regulate DNA repair genes remain to be elucidated. However, our results lend further promise to the concept of miRNAs as a tool to study the regulation of DRC. We see potentialfuture applications in prognosis and therapy of women with BC. Supported by grants S06 GM008239-20 and 1SCA157250 from the NCI Center to Reduce Health Disparities and NIH-MBRS Program (NIGMS) and NIH-NIGMS #GM082406 (CO). Citation Format: Jaime Matta, Clara Isaza, Carmen Ortiz, Erick Suarez, Luisa Morales. miRNAs associated with DNA repair capacity in Puerto Rican women with breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-06-05.