Abstract

BackgroundMicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes. Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. The aim of this study was to elucidate the role of hsa-miR-3651 for predicting of local control (LC) in early breast cancer.ResultsBy means of high-throughput technology, hsa-miR-3651 was found to be differentially expressed between patients who experienced local relapse compared to those without (N = 23; p = 0.0035). This result could be validated in an independent cohort of 87 patients using RT-qPCR (p < 0.0005). In a second analysis step with a chip-based microarray containing 70,523 probes of potential target molecules, FERM domain protein 3 (FRMD3) was found to be the most down-regulated protein (N = 21; p = 0.0016). Computational analysis employing different prediction algorithms revealed FRMD3 as a likely downstream target of hsa-miR-3651 with an 8mer binding site between the two molecules. This could be validated in an independent patient set (N = 20, p = 0.134).ConclusionThe current study revealed that hsa-miR-3651 is a predictor of LC in early breast cancer via its putative target protein FRMD3. Since microRNAs interfere in multiple pathways, the results of this hypothesis generating study may contribute to the development of tailored therapies for breast cancer in the future.

Highlights

  • MethodsThe breast cancer mortality rate in Europe is predicted to be 13.4 per 1,00,000 for 2020 [1]

  • Therapeutic advances in all disciplines related to breast conserving therapy (BCT) have led to low local relapse rates, with age being the most important predictor

  • FERM domain protein 3 (FRMD3) was identified as a putative target that interferes with protein binding as well as cytoskeletal and cell membrane stability

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Summary

Introduction

MethodsThe breast cancer mortality rate in Europe is predicted to be 13.4 per 1,00,000 for 2020 [1]. MicroRNAs are small non-coding RNAs with pivotal regulatory functions in multiple cellular processes Their significance as molecular predictors for breast cancer was demonstrated in the past 15 years. Results By means of high-throughput technology, hsa-miR-3651 was found to be differentially expressed between patients who experienced local relapse compared to those without (N = 23; p = 0.0035) This result could be validated in an independent cohort of 87 patients using RT-qPCR (p < 0.0005). Computational analysis employing different prediction algorithms revealed FRMD3 as a likely downstream target of hsa-miR-3651 with an 8mer binding site between the two molecules. This could be validated in an independent patient set (N = 20, p = 0.134). Since microRNAs interfere in multiple pathways, the results of this hypothesis generating study may contribute to the development of tailored therapies for breast cancer in the future

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