Chemotherapy-Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR Activation.

ABSTRACT: Senescence is associated with tumor metastasis and chemotherapy resistance, yet the mechanisms remain elusive. Here, it is identified that nasopharyngeal carcinoma (NPC) patients who developed distant metastasis are characterized by senescence phenotypes, in which circWDR37 is a key regulator. CircWDR37 deficiency limits cisplatin or gemcitabine-induced senescent NPC cells from proliferation, migration, and invasion. Mechanistically, circWDR37 binds to and dimerizes double-stranded RNA-activated protein kinase R (PKR) to initiate PKR autophosphorylation and activation. Independent of its kinase activity, phosphorylated PKR induces I-kappaB kinase beta (IKKβ) phosphorylation, binds to and releases RELA from NF-κB inhibitor alpha (IκBα) to trigger nuclear factor kappa B (NF-κB) activation, t

SUBMITTER: Li Q 

PROVIDER: S-EPMC10015868 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature