A novel oncogene URG4/URGCP and its role in cancer.

Oncogenes are mutated form of normal cellular genes called as proto-oncogenes and conduce to the cancer development process. Despite the fact that so many genes have been described, new genes with oncogenic characteristic and potential or tumor supressoring activity are still being defined. Recently, Up-regulated gene 4/Upregulator of cell proliferation (URG4/URGCP), a novel gene, induced by hepatitis-Bvirus-encoded X antigen (HBxAg), has been identified. URG4/URGCP gene was registered to the National Center for Biotechnology Information-GenBank (NCBI-GenBank, Entrez GeneID: 55665 and Entrez Nucleotide ID NM_017920). URG4/URGCP is located on the short arm of chromosome 7 (7p13) and synthesizes a protein containing 922 amino acids in the cytoplas. Relationship between URG4/URGCP expression and clinicopathologic characteristics were evaluated and significant results were in various cancer types such as hepatocellular carcinoma, osteosarcoma, nasopharyngeal carcinoma, bladder cancer, gastric cancer and glioma. Although, biological activity of URG4/URGCP and its effect mechanism in malignant cells is not fully understood, all interesting and promising results shows that URG4/URGCP may be a putative oncogene that contributes to multistep carcinogenesis, cell cycle regulation and other important biological process in the cell.

Investigation of the effects of a sulfite molecule on human neuroblastoma cells via a novel oncogene URG4/URGCP.

AIM: The aim of this study is to determine the anticancer effect of sulfite on SH-SY5Y neuroblastoma cells in vitro conditions and elucidate underlying molecular mechanism of sulfite and explore its therapeutic activity. MAIN METHODS: In this study, cytotoxic effects of sulfite in SH-SY5Y cels were detected over time in a dose dependent manner with the IC50 doses ranging from 0.5 to 10 mM. Genotoxic effect of sulfite was shown by comet assay. IC50 doses in the SH-SY5Y cells were detected as 5 mM. Expression profiles of the target genes related to apoptosis and cell cycle control were determined by quantitative RT-PCR. Protein changes were determined by western blot analysis. KEY FINDINGS: URG4/URGCP, CCND1, CCND2, CDK4, CDK6, E2F4 and BCL-2 gene expression levels were significantly reduced and RB1, TP53, BAX, BID, CASP2, CASP3, CASP9 and DIABLO gene expressions were significantly increased in dose group cells. The mechanism of this result may be related to sulfite dependent inhibition of cell cycle at the G1 phase by down-regulating URG4/URGCP or CCND1, CDK4, CDK6 gene expression and stimulating apoptosis via the intrinsic pathway. Sulfite suppressed invasion and colony formation in SH-SY5Y cell line using matrigel invasion chamber and colony formation assay, respectively. SIGNIFICANCE: It is thought that sulfite demonstrates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis s, invasion, and colony formation on SH-SY5Y cells. Sulfite may be an effective agent for treatment of neuroblastoma as a single agent or in combination with other agents.