Polyamine-mediated post-transcriptional regulation of COX-2

Abstract

Polyamines are involved in various cellular processes including embryonic development, cell growth and cell cycle regulation, apoptosis and carcinogenesis. Growing evidence suggests the importance of RNA processing and stability mediated by oncogenes and tumor suppressor genes in the development of cancer. Polyamines, which are found to be increased in neoplastic cells and tissues compared to normal, bind to RNA to influence its structure and function. Polyamines mediate RNA processing through the spermidine-regulated protein, eIF-5A. To further investigate how polyamines influence RNA expression, we characterized the polyamine-dependent RNA expression of a cancer-related gene, cyclooxygenase-2 (COX-2), which contains eIF-5A consensus binding elements. Depletion of polyamines by DL-alpha-difluoromethylornithine (DFMO) treatment caused an induction of COX-2 mRNA steady-state levels. Polyamines appear to regulate expression of COX-2 by a post-transcriptional mechanism.