CCR4-NOT transcription complex subunit 4 (CNOT4) and RNA polymerase II-associated factor, homolog (Saccharomyces cerevisiae) (PAF1) are implicated in nonsmall cell lung cancer (NSCLC). However, the molecular mechanism of their interaction in NSCLC progression is unknown. The expression of PAF1 and CNOT4 in human NSCLC tissues was detected by quantitative polymerase chain reaction. A549 cells that stably expressed CNOT4 and/or PAF1 were established. Western blot analysis and co-immunoprecipitation experiments were performed to reveal the interaction between CNOT4 and PAF1. Proliferation, migration, epithelial-mesenchymal transition (EMT), and colony formation assays were performed to determine the effect of CNOT4-PAF1 axis on NSCLC metastasis and stemness. Xenograft mouse tumor model was established, and tumor progression, EMT, and stemness were evaluated. It was found that CNOT4 expression was downregulated, whereas PAF1 expression was upregulated in human NSCLC tissues. CNOT4 facilitated the ubiquitination and degradation of PAF1 via the 26S proteasome. CNOT4 overexpression inhibited NSCLC progression, whereas PAF1 overexpression enhanced the proliferation, migration, and stemness of NSCLC, both in vitro and in vivo. Our results suggest that CNOT4-PAF1 axis modulates NSCLC metastasis and stemness, and may serve as potential therapeutic targets for lung cancer treatment.
Keywords: CNOT4; NSCLC; PAF1; stemness; ubiquitination.
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