Abstract 3120: miR-489 function as tumor suppressor miRNA by targeting HER2 in HER2-positive breast cancer

Abstract

Abstract Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase overexpressed in 20-30% of all breast cancer and associated with poor prognosis and outcome. Previous studies have shown that dysregulation of several micro RNAs (miRs), play a key role in breast cancer progression and metastasis. In this study, we evaluated ∼330 miRs, to find specific miRs dysregualted by HER2 signaling. After further screening we focused our study on miR-489, whose expression was ∼6-7 fold downregulated specifically by HER2 signaling. Restoration of miR-489 expression in several HER2-positive breast cancer cell lines resulted in increased cell death and cell cycle arrest. To investigate the molecular mechanism of action of miR-489, we studied effect of miR-489 on HER2 signaling pathway and found that higher expression of miR-489 led to the decreased levels of HER2 (both mRNA and protein) and decreased Akt activation. Furthermore, we for the first time demonstrated that HER2 is a direct target of miR-489 and therefore HER2 and miR-489 signaling pathways form a mutual regulatory loop. To further demonstrate clinical relevance of miR-489, we analyzed both normal and tumor human breast tissue samples using Fluorescent in situ hybridization technique (FISH). Our imaging data indicated that miR-489 is expressed at much lower level in tumor tissues compared to that of the normal breast tissue. Overall, our data indicates that miR-489 acts as a tumor suppressor miR at least partially by directly targeting HER2 in HER2 positive breast cancer cells. Citation Format: Yogin Patel, Nirav Shah, Racheal Botbyl, Jishin Lee, Hexin Chen. miR-489 function as tumor suppressor miRNA by targeting HER2 in HER2-positive breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3120. doi:10.1158/1538-7445.AM2015-3120