RESUMEN
Up-regulated gene 4 (URG4), stimulated by HBxAg, is a novel gene located on chromosome 7 (7p13). The full-length URG4 clone is 3.607 kb and encodes a polypeptide of 922 amino acids, with a molecular weight of 104 kDa (GeneID: 55665). It promotes cell growth, growth factor-independent survival, and anchorage-independent growth in HepG2 cells, and it accelerates tumor formation in nude mice. Hence, URG4 may be a natural effector of HBxAg and a putative oncogene that contributes to multi-step hepatocarcinogenesis. Cyclin D1 is frequently over-expressed in hepatocellular carcinoma, exhibiting a number of malignant phenotypes. We found that down-regulation of URG4 through RNA interference-mediated silencing suppressed cell proliferation in HepG2 cells. Over-expression of URG4 up-regulated cyclin D1 mRNA expression, whereas RNA interference-mediated URG4 silencing diminished cyclin D1 mRNA expression in HepG2 cells. The data suggest that URG4 may play an important role in the development of hepatocellular carcinoma by partially regulating the expression of cyclin D1 and has potential for use as a therapeutic target for hepatocellular carcinoma.
Asunto(s)
Ciclina D1/genética , Proteínas de Neoplasias/genética , Interferencia de ARN/fisiología , ARN Mensajero/genética , Proliferación Celular , Silenciador del Gen/fisiología , Células Hep G2 , Humanos , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
This study tests the hypothesis that woodchuck hepatitis virus encoded X-antigen expression correlates with viral replication, with hepatitis, or with both. Paired liver and serum samples from each of 55 infected woodchucks were used. Seven of 8 carriers with high levels of viral DNA in serum also had X-antigen in serum. In contrast, the frequency of X-antigen in serum was low among infected woodchucks that did not have viral surface antigen in the serum. Statistical analysis showed a significant relationship between X-antigen in serum and markers of viral replication. Woodchuck hepatitis X-antigen (WHxAg) expression in liver but not serum of carriers closely correlated with the presence of hepatitis. The finding of X-antigen in the liver of infected animals with hepatitis that cleared the virus surface antigen from serum also suggests that X-antigen is associated with ongoing hepatitis. Hence, the persistence of WHxAg in serum may signal continuing viral replication and, in liver, may contribute to the pathogenesis of chronic infection.