Looking for Tumor Specific Promoters In Silico

Abstract

—Previously we demonstrated the tumor-specific activity of several human native and chimeric promoters. Here we have analyzed the DNA sequences of experimentally tested tumor-specific promoters for the presence of recognition matrices of transcription factors and for de novo motif discovery. CiiiDER and MEME Suite software tools were used for this purpose. A number of transcription factor matrices have been identified, which are present more often in tumor-specific promoters than in the promoters of housekeeping genes. New promoter–TF regulatory relationships have been predicted by pathway analysis. A motif of 44 bp characteristic of tumor-specific promoters but not of housekeeping gene promoters has been discovered. The search through 29 598 human promoters from the EPDnew promoter database has revealed a series of promoters with this motif, their genes being associated with unfavorable prognoses in cancer. We suppose that some of these promoters may possess a tumor specific activity. In addition, a close similarity in nucleotide motifs between the promoters of the BIRC5 and MCM2 genes has been shown. The results of the study may contribute to understanding the peculiarities of gene transcription in tumors, as well as to searching for native tumor-specific promoters or creating artificial ones for cancer gene therapy, as well as in the development of anticancer vaccines.