Abstract 3950: The role of microRNA-130a in regulating HOXA5 expression in breast cancer progression
Authors: Malathi Banda, Cecilia L. Speyer, David H. Gorski
Journal: Cancer Research (2011)

Abstract Introduction: Micro RNAs (miRNAs) are key post -transcriptional and translational regulators of gene expression and regulate diverse physiological activities involving development, cell growth, differentiation, apoptosis, and pathological processes such as heart disease and cancer. In tumorigenesis miRNAs function as oncogenes or tumor suppressors. HOXA5 belongs to the family of homeobox (HOX) genes, which encode a highly conserved family of transcription factors that are known to regulate body patterning during embryogenesis. HOXA5 plays a major role in mesenchymal-epithelial interactions during organogenesis. Sukumar et al have demonstrated that HOXA5 loss of function leads to loss of p53 expression in mammary epithelial cells, which in turn contributes to malignant transformation, which is why understanding the mechanisms by which HOXA5 expression is dysregulated in breast cancer is critical. We identified a consensus binding sequence for miR-130a in the 3′-UTR of the HOXA5 coding region. Previous studies in our laboratory have shown that miR-130a downregulates HOXA5 expression in vascular endothelial cells. In this study we characterize the role of miR130a in downregulating HOXA5 expression that in turn can decrease p53 expression and function in breast cancer cells resulting in tumor proliferation, progression and metastasis. Methods: We determined whether mitogenic factors in serum affect miR130a and HOXA5 mRNA expression in the breast epithelial cell line MCF10A. Correlation between the expression of miR130a and HOXA5 mRNA expression in the MCF-10 breast progression series cell lines that model the progression from normal mammary epithelium (MCF-10A), ductal carcinoma in situ (MCF10.DCIS.com), to fully malignant (MCF10.CA1) was examined. In addition, we silenced miR-130a using a specific 2’-O-methyl-modified inhibitor and determined whether knocking it out increases HOXA5 mRNA expression in MCF10A cells. The expression levels of miR130a and HOXA5 were measured using quantitative reverse transcriptase real time PCR (QRT-PCR). Results: First, we observed that miR130a expression increases by 2.2 fold and HOXA5 mRNA levels decreases by 0.2 fold following treatment with 5% horse serum in MCF10A cells. Next, we noted that miR-130a expression increases and HOXA5 mRNA expression decreases as tumorigenicity increases in MCF10A progression series cell lines. Finally, knocking out miR-130a activity increased HOXA5 mRNA expression in MCF10A cells, demonstrating that HOXA5 is regulated by miR130a in these cells. Conclusion: Overall our results indicate that miR130a regulates HOXA5 in breast cancer cells and thus may have a role in breast tumor progression. This study will enable us to decipher the role of mir130a in breast tumor progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3950. doi:10.1158/1538-7445.AM2011-3950