Abstract B10: Overexpression of the lncRNA PVT1 contributes to the cervical cancer phenotype, possibly via association with nucleolin

Abstract

Abstract The plasmacytoma variant translocation 1 gene (PVT1) is an lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Although the mechanism by which PVT1 influences disease processes has been studied in multiple cancer types, its role in cervical tumorigenesis remains unknown. Thus, the present study was designed to investigate the role of PVT1 in cervical cancer in vitro and in vivo. PVT1 expression was measured by quantitative PCR (qPCR) in 121 invasive cervical carcinoma (ICC) samples, 19 normal cervix samples, and a cervical cell line (SiHa). Further, we used targeted knockdown in conjunction with functional assays to examine PVT1's effects on cervical cancer cell proliferation, migration and invasion, apoptosis, and cisplatin resistance. Our results demonstrate that PVT1 expression is significantly increased in ICC tissue versus normal cervix. PVT1 knockdown in cervical cancer cell lines resulted in significantly decreased cell proliferation, migration and invasion. Further, apoptosis and cisplatin cytotoxicity were significantly increased in PVT1 siRNA-transfected cells. Finally, we show that PVT1 associates with Nucleolin protein and may aid in its stabilization of GADD45A mRNA providing a possible mechanism by which PVT1 overexpression drives cervical carcinogenesis. Citation Format: Marissa Iden, Samantha Fye, Keguo Li, Tamjid Chowdhury, Ramani Ramchandran, Janet S. Rader. Overexpression of the lncRNA PVT1 contributes to the cervical cancer phenotype, possibly via association with nucleolin. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr B10.