Abstract
Abstract Although it is becoming increasingly clear that long non-coding RNAs (lncRNAs) are intricately involved in numerous cancer types, the mechanisms by which they influence carcinogenesis remain poorly understood. The plasmacytoma variant translocation 1 gene (PVT1) is a lncRNA that has been designated as an oncogene due to its contribution to the phenotype of multiple cancers. Further, our lab has recently demonstrated that human papillomavirus (HPV) integration, a hallmark of invasive cervical cancer (ICC), into the PVT1 locus occurs in multiple cervical tumors. The present study was designed to investigate the role of PVT1 in cervical carcinogenesis. PVT1 expression was measured by quantitative PCR (qPCR) in 41 ICC samples, 20 normal cervix samples, and four cervical cell lines (SiHa, HeLa, DoTc2, and E6/E7-transformed ectocervical epithelial cells). Further, we used siRNA-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. Collectively, our data suggest that PVT1 may play a crucial role in cervical carcinogenesis. Future work will focus on determining the mechanism(s) by which this lncRNA exerts its multiple effects on cancer-related processes. Citation Format: Marissa Iden, Samantha Fye, Ramani Ramchandran, Janet S. Rader. Overexpression of the long non-coding RNA PVT1 and its role in cervical carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 149. doi:10.1158/1538-7445.AM2015-149
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