MicroRNA Roles in the Nuclear Factor Kappa B Signaling Pathway in Cancer

Abstract

Nuclear factor kappa B (NF-κB) is a pluripotent and crucial dimer transcription factor that orchestrates various physiological and pathological processes, especially cell proliferation, inflammation, and cancer development and progression. NF-κB expression is transient and tightly regulated in normal cells, but it is activated in cancer cells. Recently, numerous studies have demonstrated microRNAs (miRNAs) play a vital role in the NF-κB signaling pathway and NF-κB-associated immune responses, radioresistance and drug resistance of cancer, some acting as inhibitors and the others as activators. Although it is still in infancy, targeting NF-κB or the NF-κB signaling pathway by miRNAs is becoming a promising strategy of cancer treatment.

Keywords: cancer; microRNAs; molecular therapy; nuclear factor kappa B; nuclear factor kappa B-associated resistance.

Figure 1

Structure of nuclear factor kappa B (NF-κB) and its activation mechanisms. (A) Homodimerization and heterodimerization of NF-κB1. Homodimer p50 lacks transcriptional activation domains and is unable to bind to DNA. Heterodimers are repressed by IκB. (B) Homodimerization and heterodimerization of NF-κB2. Homodimer p52 lacks transcriptional activation domains and is unable to bind to DNA. Heterodimers are repressed by IκB. (C) Classical pathway of NF-κB activation. This pathway is mediated by IκB kinase complex (IKK), leading to phosphorylation and degradation of IκB. (D) Alternative pathway of NF-κB activation. This pathway involves IKKα activation via NF-κB-inducing kinase (NIK) and induces the phosphorylation of p100, leading to the generation and translocation of p52.

Figure 2

A role of microRNAs (miRNAs) in the nuclear factor kappa B (NF-κB) signaling pathways. These two pathways rely on tumor necrosis factor (TNF), toll-like, interleukin (IL)-1, and EGF receptors (A), and BAFF reporter and CD40 (B), respectively, and they are activated or repressed by miRNAs. Activated NF-κB promotes or restrains the expression of tumor-associated genes.