The carbon catabolite repressor 4-negative on TATA (CCR4-NOT) complex, abbreviated CNOT, has deadenylation and 3'-5' exonuclease activity, mediates deadenylation in the degradation of RNA, initiates the exonuclease degradation pathway, and participates in tumor gene regulation. CNOT proteins comprise a family of global transcriptional regulators that are evolutionarily conserved in eukaryotic cells. Several subunit types of the CNOT complex have been discovered; however, little is known about the role of different subunits in tumorigenesis and development. We observed overexpression of CNOT1-11 in liver cancer and correlations with clinicopathological characteristics. The expression of some CNOTs subunits was associated with histological grades, lymph node metastasis, and tumor stages in patients with hepatocellular carcinoma (HCC). Our data suggested that some CNOTs can be used as predictors of poor prognosis in HCC patients. At the same time, we conducted an analysis of CNOTs mutations in HCC patients. Moreover, we selected CNOT6, CNOT10, and CNOT11 for protein interaction network analysis and Gene Ontology enrichment analysis to investigate their related biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Finally, the results of western blot and quantitative reverse transcription-PCR (qRT-PCR) experiments were consistent with the database findings. Results of this study suggest that CNOT6, CNOT10, and CNOT11, acting as regulators of transcription, may play an important role in the development of HCC and may serve as biological markers in the diagnosis and prognosis of HCC.
Keywords: CNOT; clinicopathological features; hepatocellular carcinoma; prognosis.