Cleavage and polyadenylation specific factor 4 targets NF-κB/cyclooxygenase-2 signaling to promote lung cancer growth and progression.

摘要: Overexpression of cyclooxygenase 2 (COX-2) is frequently found in early and advanced lung cancers. However, the precise regulatory mechanism COX-2 cancers remains unclear. Here we identified cleavage polyadenylation specific factor 4 (CPSF4) as a new for demonstrated role CPSF4/COX-2 signaling pathway regulation cancer growth progression. or knockdown CPSF4 up-regulated suppressed expression at mRNA protein levels, promoted inhibited cell proliferation, migration invasion cells. Inhibition induction reversed CPSF4-mediated growth. Cancer cells with overexpression exhibited increased decreased p-IKKα/β p-IκBα, translocation p50/p65 from cytoplasm to nucleus, binding p65 on promoter region. In addition, was bind sequences directly activate transcription COX-2. Silencing NF-κB blockade activity abrogated promoter, thereby attenuated up-regulation Moreover, promote tumor progression by up-regulating xenograft mouse model. mice, while such mediated could be rescued through inhibition activation signaling. Correspondingly, also elevated tissues treatment inducer LPS inhibitor this elevation attenuation. Furthermore, showed that positively correlated levels patients. Simultaneous high proteins predicted poor prognosis patients Our results therefore novel transcriptional cancer, offer potential therapeutic target bearing aberrant