Study of the antisense transcript to AFAP1 human gene

Antisense regulation of gene expression is a widespread but not well-understood mechanism of gene expression regulation. Recently we have carried out a whole genome in silico search of cis-antisense clusters of transcripts in humans. The developed database revealed a significant number of sense—antisense pairs consisting of one EST cluster expressed predominantly in normal tissues and another cluster with tumor-specific expression. The role of antisense transcripts in the regulation of oncogenes and tumor suppressor genes warrants functional research. Here we describe and characterize an antisense mRNA asAFAP overlapping human AFAP1 gene. AFAP1 encodes for an actin filament binding protein, which serves as a modificator of actin filament structure and integrity. It also is able to relay a signal from receptor tyrosine kinases through PKCα to Src protein kinase. It has been shown that AFAP1 is overexpressed in prostate cancer and contributes to tumorigenic growth. We hypothesized that the transcription of asAFAP antisense mRNA may lead to suppression of sense AFAP1 gene expression and a compensatory restraint added to one of the mitogenic signaling pathway that is unlikely to be supported by natural selection in the tumor cell population. To study the intriguing phenomenon of tumor-specic asAFAP antisense expression we performed detailed in silico analysis of asAFAP sequences and experimentally quantified this transcript in normal and tumor human tissues. We have specified the exon-intronic structure of asAFAP antisense transcript and carried out the expression analysis of AFAP1 sense—antisense pair in normal and tumor human tissues.