In Silico Analysis of the CST6 Tumor Suppressor Gene

Abstract

The gene encoding cystatin E/M, CST6, is a Class II tumor suppressor. Using bioinformatics tools for database mining and virtual gene expression profiling, the authors showed that CST6 is differentially expressed in various types of cancer. Moreover, epigenetic silencing mediated by hypermethylation of the CpG island located at the CST6 promoter was found to be conserved in mammalian species. Comprehensive analyses of animal genomes led to the identification of novel CST6 transcript orthologs and splice variants that enabled us to trace the evolutionary origin of CST6. Moreover, eight novel and potentially regulatory SNPs were identified in CST6 gene. Conserved cancer-relevant regulatory elements were identified in the CST6 gene promoter. In addition, miRNAs that are differentially expressed in human cancers were identified as putative posttranscriptional regulators of CST6. Collectively, the authors suggest that expression of CST6 in normal and cancer cells is coordinately regulated by genomic, transcriptional and post-transcriptional mechanisms.