Abstract 126: miR-221 promotes tumorigenesis in human triple negative breast cancer cells

Abstract

Abstract MicroRNAs (miRNAs) are non-coding, single-stranded RNAs of ∼22 nucleotides that act as agents of the RNA interference pathway and negatively regulate their targets by either cleaving mRNA molecules or by inhibiting their translation. miRNAs are frequently located at fragile sites and genomic regions susceptible to amplification, deletion, or translocation during tumor development, and growing evidence indicates that miRNAs can function as tumor suppressors and oncogenes. Additionally, miRNA expression profiling analyses have revealed characteristic miRNA signatures in human cancers. MicroRNA-221 (miR-221) is up-regulated in many cancers including HCC, glioblastoma, pancreatic cancer, prostate cancer, and tamoxifin-resistant breast cancer. Overexpression of miR-221 has previously been shown to promote cancer cell proliferation, most likely by its ability to modulate the expression of the oncogenic proteins c-kit and cyclin dependent kinase inhibitor (CDKI) CDKN1B/p27. In this study, we demonstrate that in comparison to normal mammary tissues, miR-221 is overexpressed in triple negative breast cancer cell lines (TNBC) and downregulated in non-TNBC breast cancer cell lines. Stable knockdown of miR-221 expression reduced cell proliferation and induced apoptosis in TNBC cell lines. Overexpression of miR-221 promoted cell migration and cell invasion, while knockdown of miR-221 inhibited both cell migration and cell invasion and increased E-cadherin expression in TNBC lines but not in the non-TNBC lines. Furthermore, downregulation of miR-221 in MDA-MB-231 xenografts decreased the tumor growth rate in mice. Therefore, our results suggest that miR-221 is a potential oncomiR that promotes cell proliferation, migration, and invasion in triple negative breast cancer cells, and that knockdown of miR-221 is able to induce in vitro and in vivo anti-tumor activity in these TNBC cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 126. doi:1538-7445.AM2012-126