Abstract 5345: MicroRNA mediated regulation of a novel gene, MIEN1, in cancer metastasis.

Abstract

Abstract Migration and invasion enhancer gene 1(MIEN1), previously known as C17orf37, C35, ORB3, XTP4, RDX12, and MGC14832, is located in the 17q12 region of the human chromosome. MIEN1 expression is minimal to negligible in normal cells and tissues compared to its abundant expression in various cancers, including breast, prostate, oral and gastrointestinal carcinomas. MIEN1 works as a signaling molecule through the AKT/NF-κB pathway by up-regulating key proteases, matrix metalloproteinase - 9, urokinase - type plasminogen activator and vascular endothelial growth factor. We have shown that MIEN1 plays an important role in the migration and invasion of cancer through increased filopodia formation, hence promoting metastasis. The overall objective of this study is to identify the mechanisms that lead to the differential regulation of MIEN1 between normal and cancer cells. Our hypothesis is that MIEN1 is post-transcriptionally regulated by specific microRNA(s) that is (are) down-regulated in cancer, thus explaining its aberrant increased expression in cancer. MicroRNA expression profiling pattern predict several microRNAs that can directly bind to 3′UTR of MIEN1 mRNA. In silico analysis followed by northern blotting and real time PCR indicate a novel microRNA that regulates MIEN1 expression. This was further confirmed by decrease or increase in RNA and protein levels of MIEN1 as well as its downstream signaling effectors, upon microRNA mimic or inhibitor addition, respectively. Direct binding of the microRNA with MIEN1 mRNA was further confirmed by luciferase reporter assays, while the scratch wound healing and tumor invasion assays showed the functional significance of this microRNA on migration and invasion. Since the importance of MIEN1 as a key signaling molecule in cancer is well established, understanding the mechanism(s) involved in the regulation of MIEN1 will aid in designing novel and effective therapeutic strategies to treat cancer patients. Citation Format: Smrithi Rajendiran, Jamboor K. Vishwanatha. MicroRNA mediated regulation of a novel gene, MIEN1, in cancer metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5345. doi:10.1158/1538-7445.AM2013-5345