ORAOV1 -A Correlates with Poor Differentiation in Oral Cancer

Abstract

Oral cancer overexpressed 1 (ORAOV1) is a crucial oncogene in oral squamous cell carcinoma (OSCC). In this study, we have identified a novel splice variant of ORAOV1, designated as ORAOV1-A. To study the potential role of ORAOV1-A in OSCC, we tested its expression in 7 OSCC cell lines, as well as in 19 normal oral tissue samples and 47 OSCC tissue samples. The expression of ORAOV1-A was detectable in 6 out of 7 OSCC cell lines tested. In OSCC tissue samples, the expression frequency of ORAOV1-A (51.1%) was much higher than that in normal samples (10.5%). Notably, an inverse correlation was found between the expression frequency of ORAOV1-A and the degree of differentiation in OSCC (P = 0.0017). In conclusion, our results suggested that ORAOV1-A may play a functional role in the tumorigenesis of OSCC, and ORAOV1-A expression may serve as an adjunctive prognostic indicator for persons with OSCC.

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References

Black DL -2003-. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 72:291–336.

Chang JT, Wang HM, Chang KW, Chen WH, Wen MC, Hsu YM, et al. -2005-. Identification of differentially expressed genes in oral squamous cell carcinoma -OSCC-: overexpression of NPM, CDK1 and NDRG1 and underexpression of CHES1. Int J Cancer 114: 942–949.

Choi S, Myers JN -2008-. Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res 87:14–32.

Engels K, Knauer SK, Metzler D, Simf C, Struschka O, Bier C, et al. -2007-. Dynamic intracellular survivin in oral squamous cell carcinoma: underlying molecular mechanism and potential as an early prognostic marker. J Pathol 211:532–540.

Etoh T, Kanai Y, Ushijima S, Nakagawa T, Nakanishi Y, Sasako M, et al. -2004-. Increased DNA methyltransferase 1 -DNMT1- protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. Am J Pathol 164:689–699.

Faustino NA, Cooper TA -2003-. Pre-mRNA splicing and human disease. Genes Dev 17:419–437.

Garcia-Blanco MA, Baraniak AP, Lasda EL -2004-. Alternative splicing in disease and therapy. Nat Biotechnol 22:535–546.

Holmila R, Fouquet C, Cadranel J, Zalcman G, Soussi T -2003-. Splice mutations in the p53 gene: case report and review of the literature. Hum Mutat 21:101–102.

Honda K, Yamada T, Seike M, Hayashida Y, Idogawa M, Kondo T, et al. -2004-. Alternative splice variant of actinin-4 in small cell lung cancer. Oncogene 23:5257–5262.

10.

Huang X, Gollin SM, Raja S, Godfrey TE -2002-. High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells. Proc Natl Acad Sci USA 99:11369–11374.

11.

Jiang L, Zeng X, Yang H, Wang Z, Shen J, Bai JP, et al. -2008-. Oral cancer overexpressed 1 -ORAOV1-: a regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma. Int J Cancer 123: 1779–1786.

12.

Lewin F, Norell SE, Johansson H, Gustavsson P, Wennerberg J, Biorklund A, et al. -1998-. Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck. Cancer 82:1367–1375.

13.

Maniatis T, Tasic B -2002-. Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418:236–243.

14.

Massiello A, Salas A, Pinkerman RL, Roddy P, Roesser JR, Chalfant CE -2004-. Identification of two RNA cis-elements that function to regulate the 5′ splice site selection of Bcl-x pre-mRNA in response to ceramide. J Biol Chem 279:15799–15804.

15.

Miller CS, Johnstone BM -2001-. Human papillomavirus as a risk factor for oral squamous cell carcinoma: a meta-analysis, 1982–1997. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91:622–635.

16.

Neville BW, Day TA -2002-. Oral cancer and precancerous lesions. CA Cancer J Clin 52:195–215.

17.

Pagani F, Baralle FE -2004-. Genomic variants in exons and introns: identifying the splicing spoilers. Nat Rev Genet 5:389–396.

18.

Scully C -2002-. Oral squamous cell carcinoma: from a hypothesis about a virus to concern about possible sexual transmission. Oral Oncol 38:227–234.

19.

Venables JP -2004-. Aberrant and alternative splicing in cancer. Cancer Res 64:7647–7654.

20.

Wang Z, Jiang L, Huang C, Li Z, Chen L, Gou L, et al. -2008-. Comparative proteomic approach to screening of potential diagnostic and therapeutic targets for oral squamous cell carcinoma. Mol Cell Proteomics 7:1639–1650.

21.

Xia J, Chen QM, Li BQ, Zeng X -2007-. Amplifications of TAOS1 and EMS1 genes in oral carcinogenesis: association with clinicopathological features. Oral Oncol 43:508–514.

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