Oral cavity cancer (OCC) is the most common cause of cancer-related death worldwide and shows poor clinical outcome after standard therapies. Therefore, new prognostic biomarkers and therapeutic targets for OCC are urgently awaited. This study aims to identify novel prognostic biomarkers or therapeutic targets for OCC. To screen the new prognostic biomarkers and therapeutic targets for OCC, we selected from our original gene expression database up-regulated in oral cancer 1 (UROC1) that appeared to encode cytoplasmic protein as a candidate. Immunohistochemical analysis using tissue microarray covering 99 OCC tissues confirmed that UROC1 protein was expressed in 67 cases (68%) of 99 OCC tissues, but not in normal oral epithelia. High levels of UROC1 expression was significantly associated with poorer prognosis for OCC patients (P = 0.0299, log-rank test). In addition, knockdown of endogenous UROC1 expression by siRNAs significantly inhibited the growth and invasion of OCC cells, whereas the induction of exogenous UROC1 expression enhanced the growth and invasive ability of OCC cells. In addition, flow cytometric analysis and various apoptosis assays of these tumor cells transfected with siRNAs for UROC1 revealed a significant induction of apoptosis. Assays using phosphor-antibody array and lysates from cells transfected with siRNAs or plasmid for UROC1 and subsequent functional analyses revealed that UROC1 could regulate the growth, survival, and invasion of OCC cells probably through activation of insulin-like growth factor 1 receptor (IGF1R) pathway. These data suggest that UROC1 could be a novel prognostic biomarker and a therapeutic target for OCC.
Citation Format: Thang Manh Phung, Atsushi Takano, Yoshihiro Yoshitake, Masanori Shinohara, Yohinori Murakami, Yataro Daigo. Characterization of UROC1 protein as a novel prognostic biomarker and a therapeutic target for oral cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1274.