Abstract 5356: The role of VNN3 gene in nasopharyngeal carcinoma tumorigenesis
Authors: Huang Shang-Yu , Chen Yi-Ying , Huang Dah-yeou , Wu Cheng-Der , Lin Chin-Tarng 
Published: May 2015

Nasopharyngeal carcinoma (NPC) is one of the leading cause of cancer-related deaths in southeastern China and South East Asia. However, the detailed pathogenesis mechanisms of NPC remain to be elucidated. Despite novel therapies and advances in early detection, it is often diagnosed at an advanced stage and has a poor prognosis. Recent evidences showed that SRY (sex-determining region Y)-box 5 (SOX-5) plays an important role in Nasopharyngeal tumor development, but little is known about the role of its associated protein such as VNN3 gene (a pantetheinase) in controlling tumor development. SOX-5 overexpression enhances tumor formation in NPC, and has a poor prognosis. In this study, we compared the differential gene expression in NPC cell lines and normal nasal mucosal epithelial cells by cDNA microarray analysis, and observed that the RNA and protein expression levels of SOX-5 and VNN3 were dramatically increased in NPC cell lines than normal nasal mucosal epithelial cells by qRT-PCR and Western blot analysis. In order to investigate that whether VNN3 gene could alter NPC progression, we observed at first the gene expression in different NPC cell lines using qRT-PCR analysis and found that the expression of VNN3 in NPC cell line, especially in NPC-TW01 cell line was highly upregulated. Besides, we also found that the expression level of VNN3 protein was also increased in multiple NPC cell lines and NPC biopsy specimens by immunohistochemical staining and Western bloting. In this study, we also isolated the cancer stem cell (CSC) from NPC-TW01 cell line by conditioned culture medium, highly expression level of VNN3 gene was found in the NPC-TW01 stem cells (CSC). To further analysis of the functional role of VNN3 in this NPC and CSC lines, the expression of VNN3 was decreased to about 70-80% of the control in NPC and CSC after knockdown of VNN3 by VNN3 shRNA-lentiviral infection. This in turn resulted in a significant reduction of cell proliferation, migration and invasion abilities. We also found that a decreased expression level of VNN3 (Pantetheinase), which is an amidohydrolase that hydrolyzes pantetheine into pantothenic acid (vitamin B5) as well as cysteamine, and caused an increase of intracellular reactive oxygen species (ROS), and cell death through apoptosis; the weight of NPC xenograft tumors had diminished about 51% after 6 weeks, compared with shLuc control in SCID mice bearing NPC xenografts derived from these lentiviral infected NPC and CSC cell lines. Impairment of tumor cell proliferation, accompanied with apoptosis was found in the xenografts histopathologically. These novel findings of the functional role of VNN3 may have a potential implication in molecular targeted therapy for NPC.

Citation Format: Shang-Yu Huang, Yi-Ying Chen, Dah-yeou Huang, Cheng-Der Wu, Chin-Tarng Lin. The role of VNN3 gene in nasopharyngeal carcinoma tumorigenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5356. doi:10.1158/1538-7445.AM2014-5356