ORAOV1 (oral cancer overexpressed 1)

2009-05-01 Lu Jiang , Jinsheng Yu , Qianming Chen Affiliation

State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China (LJ, QC); School of public health, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, IL, USA (JY)

Identity

HGNC

ORAOV1

LOCATION

11q13.3

IMAGE

LOCUSID

220064

ALIAS

CIAB1,ORAOV1,TAOS1

FUSION GENES

Show Gene Fusions

DNA/RNA

Note

The ORAOV1 gene spans 9.75 Kb genomic DNA and consists of 5 known exons. The coding sequence of ORAOV1 is 414 nucleotides long.

Figure 1 : ORAOV1 gene consists of five exons and spans 9.75 kb of genomic DNA.

Figure 2 : (A) The schematic structures of the ORAOV1 gene and its two transcript variants. ORAOV1 has five exons. The two ORAOV1 splice variants consist of different exon combinations that produce different protein-coding regions. (B) Comparison of ORAOV1 with ORAOV1-A nucleotide sequence. White boxes show amino acid differences.

Transcription

So far, there is one reported transcript variant of ORAOV1 caused by alternative exon utilization. The production of transcript variant 1, which is named as ORAOV1-A, is produced by alternative splicing of exon 3. An in-frame stop codon in exon 4 indicates that the ORAOV1 protein isoform 1 may be interrupted at this position. Interestingly, an association between the expression level of this ORAOV1 gene ORAOV1-A and the differentiation degree of oral squamous cell carcinoma has been observed in a Chinese patient cohort.

Proteins

Note

So far, no study describes the location of ORAOV1 protein in cells or tissues.

Function

Apoptosis, but whether it belongs to extrinsic or intrisic pathway is yet unknown.

Implicated in

Entity name

Oral squamous cell carcinoma

Note

ORAOV1 gene may be a candidate biomarker for diagnosis and prognosis in oral squamous cell carcinoma (OSCC). This finding was made based on a study using PCR to measure ORAOV1 in 15 healthy oral mucosa tissue samples, 30 OLK tissues samples, and 33 OSCC tissue samples. The authors found that ORAOV1 amplification was significantly associated with larger tumor size, presence of lymph node metastasis, poor histological differentiation and advanced clinical stage. Therefore, they suggested the potential roles of ORAOV1 in oral carcinogenesis. Further studies about the biological functional role of ORAOV1 in OSCC tumorigenesis showed that ORAOV1 plays pivotal roles in the growth and angiogenesis of OSCC. The authors performed a loss-of-function study by using small interfering RNA (siRNA) against ORAOV1 in two OSCC cell lines. They found that the OSCC cells with reduced ORAOV1 showed retarded cell growth in vitro and displayed inhibition in both tumor growth and tumor angiogenesis in vivo. Further analyses reveal that the retarded cell growth is associated with an increase in apoptosis involving the activation of caspase 3-dependent pathway, and a cell cycle arrest at the S-phase with a downregulation of cyclin A, cyclin B1, and CDC2. The suppressed tumor growth in vivo may be attributed to synergistic effect between inhibition in cell growth and suppression of tumor angiogenesis. The latter is most likely due to a suppression of VEGF.
The study of the novel splice variant of ORAOV1, ORAOV1-A, showed that there was an inverse correlation between the expression frequency of ORAOV1-A and the degree of differentiation in OSCC. This result suggested that ORAOV1-A may play a functional role in the tumorigenesis of OSCC, and the ORAOV1-A expression may serve as an adjunctive prognostic indicator for patients with OSCC.

Entity name

Esophageal squamous cell carcinoma

Note

ORAOV1 is supposed to serve as a new marker for predicting the malignancy of esophageal SCC. This finding was made based on a study using quantitative RT-PCR to examine the ORAOV1 gene expression level in 38 esophageal SCCs. The authors found that the ORAOV1 overexpression correlated with the clinicopathological features of esophageal SCCs, which revealed a significant difference in lymph node metastasis and a trend towards advanced TNM stages.

Bibliography

Pubmed ID	Last Year	Title	Authors
17171571	2007	High-resolution mapping identifies a commonly amplified 11q13.3 region containing multiple genes flanked by segmental duplications.	Gibcus JH et al
12172009	2002	High-resolution mapping of the 11q13 amplicon and identification of a gene, TAOS1, that is amplified and overexpressed in oral cancer cells.	Huang X et al
19493886	2009	ORAOV1-A correlates with poor differentiation in oral cancer.	Jiang L et al
18688849	2008	Oral cancer overexpressed 1 (ORAOV1): a regulator for the cell growth and tumor angiogenesis in oral squamous cell carcinoma.	Jiang L et al
17065789	2006	Molecular cytogenetic characterization of the 11q13 amplicon in head and neck squamous cell carcinoma.	Jin C et al
12792807	2003	Evolutionary conservation of CCND1-ORAOV1-FGF19-FGF4 locus from zebrafish to human.	Katoh M et al
16827140	2006	TAOS1, a novel marker for advanced esophageal squamous cell carcinoma.	Komatsu Y et al
17906623	2007	Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs.	Salmon Hillbertz NH et al
17005439	2007	Amplifications of TAOS1 and EMS1 genes in oral carcinogenesis: association with clinicopathological features.	Xia J et al

Citation

Lu Jiang ; Jinsheng Yu ; Qianming Chen

ORAOV1 (oral cancer overexpressed 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-05-01

Online version: http://atlasgeneticsoncology.org/gene/41611/oraov1