Abstract 4174: Identification of PRPF4 as a novel cancer promoter through AKT signaling in lung cancer

Abstract

Abstract We recently constructed a large-scale gene expression database containing more than 33,000 tumors samples by applying cancer outlier profile analysis, and identified many candidate genes as therapeutic targets (Shin G et al., 2011). One of potential target candidates is PRPF4, which is over-expressed in a variety of human cancer, particularly in the breast, colon, ovary, skin and lung cancer patients. PRPF4 (PRP4 pre-mRNA processing factor 4 homolog), also called PRP4, HPRP4, Prp4p, or HPRP4P, is involved in pre-mRNA splicing and interacts with U4/U6-U5 tri-snRNP complex. Moreover, there have been a few studies on the roles of PRPF4 in diseases including cancer. In one study, PRPF4, along with MDR1 (ABCB1) and survivins, was involved in drug resistance in ovarian cancer patients (Duan Z et al., 2008), but its role in cancer is mostly unknown. In this study, we found that PRPF4 was over-expressed in breast, colon, and lung cancers, and involved in cancer progression, invasion, and migration, and interacted with AKT. Knock-down of PRPF4 by small interfering RNA in both lung and breast cancer cell lines dramatically reduced invasion, migration, and cell proliferation in vitro. We confirmed the up-regulation of PRPF4 in about 30% of lung and breast cancer specimens by RT-PCR. We also found that PRPF4 interacts with AKT and thus activates PI3K/AKT signaling pathway and increases proliferation, invasion, and migration of lung cancer cells. Collectively, we suggest PRPF4 is a novel up-regulated gene involved in various cancer progression and propose it as a novel cancer biomarker for targeted therapeutics. 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 4174. doi:1538-7445.AM2012-4174