Dissecting role of regulatory factors in NF-kappaB pathway with siRNA

NF-kappaB, a family of related transcription factors, has been a focus of intense scientific research during the past decade. Multiple stimuli, both extracellular and intracellular, lead to its activation. The NF-kappaB pathway regulates expression of a diverse array of genes involved in different biological processes. Various pathological states are characterized by the dysregulated NF-kappaB pathway. Recently, NF-kappaB activation has been connected with multiple aspects of oncogenesis and serves as an important mechanism to regulate cell survival in response to chemotherapy by activating different genes that inhibit apoptosis. Several methods of inhibiting NF-kappaB activation, such as antisense oligonucleotides, proteosome inhibitors and RNA interference (RNAi) are currently under investigation. RNAi represents a powerful tool to better define the role of specific genes in different signal transduction pathways and has recently been used to define the function of genes that regulate the NF-kappaB pathway. This review discusses the emerging role of RNAi to dissect the function of regulatory factors in the NF-kappaB pathway and its potential use as a targeted therapy.