Abstract 1465: Regulatory role of miRNA-661 in triple-negative breast cancer of African American women
Authors: Aline S. Fonseca, Selene Elifio-Esposito, Marilesia F. Souza, Akanksha Mahajan, Yara R. Zabala, Bruna M. Sugita, Luciane R. Cavalli
Journal: Cancer Research (2017)

Abstract Triple negative breast cancer (TNBC) disproportionately afflicts young African American (AA) women when compared to Non-Hispanic Whites (NHW), being usually diagnosed in advanced stage, likely to experience metastasis and often unresponsive to treatment. An increased number of studies have characterized the differences in the tumor biology between AA and NHW patients and have shown that breast tumors from AA patients present increased cell proliferation, elevated expression of angiogenesis markers and higher migration and invasive properties, the fundamental hallmarks of cancer. MiRNAs are short sequences of non-coding RNAs that act on gene expression regulation. In this study, our main objective was to determine the expression levels of miRNA-661 in the TNBC of AA when compared to the NHWs and to verify it is directly role in affecting the aggressive TNBC phenotype. MiRNA-661 expression analysis was conducted by RT-qPCR in the tumor tissue of 31 AA-TNBC patients and 17 NHW-TNBC patients. AA and NHW samples of 40 and 20 non-TNBC subtype, respectively, and 49 adjacent normal tissue (ANTs) were used as control for the subtype and tumor specificity, respectively. Our results showed a significant down-regulation of miR-661 expression in TNBC of AA in relation to the NWH (P&amp;lt;0.0001) and between the AA-TNBC and non-TNBC subtypes (P&amp;lt;0.001). MiR-661 was also significantly differentially expressed in the ANT when compared to the tumor tissue (P&amp;lt;0.001). In addition, ROC analysis showed a high power of this miRNA in discriminating the TNBC genome of AA and NHW women (AUC= 0.79 (0.65-0.92), 95%CI). Modulation of the expression of this miRNA in the HCC1806 and BT549 TNBC cell lines, derived from an AA and NHW patient respectively, using inducers/repressors systems, showed its direct effect in cell proliferation, migration and cytotoxicity. Interestingly these effects presented a higher impact in the HCC1806 cell line model. Altogether, our findings indicate that miRNA-661 dysregulation is associated with TNBC of AA women, and directly impacts their tumor phenotype. The uncovering of the molecular mechanisms that dictates these effects, specially the ones that modulate drug response, is critical for patient selection and stratification into novel and efficient target therapies. This much needed knowledge would lead to profound clinical benefits, particularly to young AA patients, that are commonly affected by the TNBC aggressive phenotype. Funding: This project was supported by the Georgetown University Center of Excellence in Regulatory Science and Innovation (CERSI U01FD004319), a collaborative effort between the university and the U.S. Food and Drug Administration to promote regulatory science through innovative research and education. This research does not necessarily reflect the views of the FDA. The authors thank the CNPq - Brazil for scholarship (ASF). Citation Format: Aline S. Fonseca, Selene Elifio-Esposito, Marilesia F. Souza, Akanksha Mahajan, Yara R. Zabala, Bruna M. Sugita, Luciane R. Cavalli. Regulatory role of miRNA-661 in triple-negative breast cancer of African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1465. doi:10.1158/1538-7445.AM2017-1465