Determination of the Possible Target Genes of Hepatoma-derived Growth Factor in Hepatoma Cells

Background/Aim: We identified a new growth factor, hepatoma-derived growth factor (HDGF), which is a presumed growth-stimulating factor of hepatocellular carcinoma (HCC). Recently, we identified two microRNAs (miR-6072 and miR-3137) induced by HDGF, which were also found to be associated with the prognosis of HCC patients. This study aimed to identify the target genes of these HDGF-related microRNAs. Materials and Methods: A public database was searched for candidate target genes of HDGF-related microRNAs. Using the microarray system, the genes whose expression changed in response to HDGF administration were determined. Finally, a public cancer genomics database was searched for genes that were induced by HDGF and associated with the prognosis of HCC. Results: A total of 1,132 genes were identified as common target genes of the 2 HDGF-related microRNAs. Among these genes, a microarray system showed that the expression of 6 genes was increased (>= 1.5-fold) or decreased (<= 0.67 -fold) after HDGF administration. Using a cancer genomics database, two of the six genes were found to be related to the prognosis of HCC. A high expression of alkylglycerone phosphate synthase (AGPS) was significantly associated with a poor survival (p=0.0025, 0.0063 and 0.0081 for the 1-, 3 -and 5-year survival, respectively). A high expression of the shroom family member 4 (SHROOM4) gene was found to be significantly associated with a better survival (p=0.003,0.0006 and 0.0006 for the 1-, 3-and 5-year survival, respectively). Conclusion: This study identified potential target genes of HDGF-related microRNAs that were associated with the prognosis of HCC.