Differential expression profiles of sense and antisense transcripts between HCV-associated hepatocellular carcinoma and corresponding non-cancerous liver tissue

Recent studies have demonstrated that natural antisense transcripts, whichare complementary sequences to messenger RNA, have important cellular functionssuch as the stabilization and silencing of mRNA. However, the possible contributionof antisense transcripts in hepatocellular carcinoma (HCC) development has notbeen described. Therefore, we simultaneously investigated the sense and antisensetranscripts of HCC and non-cancerous tissues to explore the possible contributionof antisense transcripts to HCC progression. RNA was prepared from 15 HCV-associatedHCCs and from 6 corresponding non-cancerous tissues and was subjected to expressionprofile analysis of sense and antisense transcripts using a human custom microarray.Differential expression of 161 sense and 25 antisense transcripts was observedwith more than 2-fold between HCC and non-cancerous tissue (p<0.001). The expressionof the sense and antisense transcripts was used to cluster cancer and non-canceroustissues, and the cancer and non-cancerous tissues were found to be clearly separatedinto different clusters. Additionally, the sense and antisense expression profileswere analyzed with regard to HCC differentiation (p<0.001), resulting in 71sense and 43 antisense transcripts. These unique transcripts did not overlap withthose found in the discrimination of HCC from non-cancerous tissues. When theHCC tissues were clustered by transcript expression, the antisense transcriptsresulted in clustering of HCC that was consistent with grouping based on histology.These findings strongly indicate that the antisense transcripts together withthe sense transcripts are involved in liver tumorigenesis.