Defining the mechanism by which IFN-|[beta]| dowregulates c-myc expression in human melanoma cells: pivotal role for human polynucleotide phosphorylase (hPNPaseold-35)

摘要: Type I interferons (IFN-α/-β) are capable of suppressing c-myc mRNA expression by modulating post-transcriptional processing. However, the molecular mechanism this phenomenon is poorly understood. We previously established that human polynucleotide phosphorylase (hPNPaseold-35), a type IFN-inducible 3′,5′ exoribonuclease involved in degradation, induces G1 cell cycle arrest and eventually apoptosis specifically degrading mRNA. now demonstrate close association between IFN-β-induced hPNPaseold-35 upregulation downregulation melanoma cells. Employing stable clones expressing small inhibitory RNA, we key molecule coupled with IFN-β-mediated Inhibition or overexpression protects cells from growth inhibition, emphasizing importance consequent inhibition induction. In these contexts, targeted might be novel therapeutic strategy for c-myc-overexpressing IFN-resistant tumors, such as melanomas.