A Constitutive Intrinsic Inflammatory Signaling Circuit Composed of miR-196b, Meis2, PPP3CC, and p65 Drives Prostate Cancer Castration Resistance.

ABSTRACT: Androgen deprivation therapy is the most effective treatment for advanced prostate cancer, but almost all cancer eventually becomes castration resistant, and the underlying mechanisms are largely unknown. Here, we show that an intrinsic constitutively activated feedforward signaling circuit composed of IκBα/NF-κB(p65), miR-196b-3p, Meis2, and PPP3CC is formed during the emergence of castration-resistant prostate cancer (CRPC). This circuit controls the expression of stem cell transcription factors that drives the high tumorigenicity of CRPC cells. Interrupting the circuit by targeting its individual components significantly impairs the tumorigenicity and CRPC development. Notably, constitutive activation of IκBα/NF-κB(p65) in this circuit is not dependent on the activation of traditional I

SUBMITTER: Jeong JH 

PROVIDER: S-EPMC5218896 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature