Abstract B41: REV7 is a possible prognostic predictor and a potential therapeutic target in human malignancy

Abstract

Abstract Human REV7 (also known as MAD2L2 and MAD2B) is involved in DNA repair, cell cycle regulation, gene transcription and carcinogenesis, and is a key protein in translesion DNA synthesis. Here, we present our study to evaluate the significance of REV7 expression in human malignancy and its possibility to be a molecular target for cancer therapy. REV7 expression was assessed in epithelial ovarian cancer (EOC) and diffuse large B-cell lymphoma (DLBCL) by immunohistochemical staining. REV7 expression was detected in the majority of EOCs (92.0%) with especially high levels of expression frequently observed in ovarian clear cell carcinomas (CCCs) (73.5%) compared with that of non-CCCs (53.4%). Enhanced immunoreactivity to REV7 was associated with poor prognosis represented by reduced progression-free survival in advanced stage (stages II to IV) EOC. REV7 expression was also assessed in DLBCL, the most common type of non-Hodgkin lymphoma, in which high REV7 expression was associated with significantly shorter overall survival and progression-free survival. The effects of REV7 knockdown on cell proliferation and chemosensitivity in CCC cells were also analyzed in vitro and in vivo. REV7 knockdown in CCC cells decreased cell proliferation without affecting cell cycle distribution. Additionally, the number of apoptotic cells and DNA damaged cells were increased after cisplatin treatment. In a nude mouse tumor xenograft model, inoculated REV7-knockdown tumors showed significantly reduced tumor volumes after cisplatin treatment compared with those of the control group. These findings indicate that high REV7 expression is associated with poor prognosis in EOC and DLBCL, and depletion of REV7 enhances sensitivity to cisplatin treatment in CCC, suggesting that REV7 is a candidate for molecular target in human malignancy. Citation Format: Yoshiki Murakumo, Kaoru Niimi, Sosei Okina. REV7 is a possible prognostic predictor and a potential therapeutic target in human malignancy [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr B41.