Zhao Haichao, Chen Changzhou, Chen Xidong, Zhang Donglin, Li Jian, Yang Chuanli, Ren Chongren, Ren Xiaojing, Fu Xifeng, Li Yanjun, He Jiefeng, Zhao Haoliang
Shanxi Medical University, Taiyuan, China.
Department of General Surgery, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China.
DNA Cell Biol. 2020 Oct 20. doi: 10.1089/dna.2020.5818.
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 in liver cancer and correlations with clinicopathological characteristics. The expression of some 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.
碳代谢物阻遏蛋白4-负性调控TATA（CCR4-NOT）复合物，简称为CNOT，具有去腺苷酸化和3'-5'核酸外切酶活性，介导RNA降解中的去腺苷酸化，启动核酸外切酶降解途径，并参与肿瘤基因调控。CNOT蛋白构成了一类在真核细胞中进化保守的全局转录调节因子家族。已发现CNOT复合物的几种亚基类型；然而，关于不同亚基在肿瘤发生和发展中的作用知之甚少。我们观察到其在肝癌中的过表达及其与临床病理特征的相关性。一些亚基的表达与肝细胞癌（HCC）患者的组织学分级、淋巴结转移和肿瘤分期相关。我们的数据表明，一些CNOT可作为HCC患者预后不良的预测指标。同时，我们对HCC患者的CNOT突变进行了分析。此外，我们选择CNOT6、CNOT10和CNOT11进行蛋白质相互作用网络分析和基因本体富集分析，以研究它们相关的生物学过程和京都基因与基因组百科全书（KEGG）通路。最后，蛋白质印迹和定量逆转录PCR（qRT-PCR）实验结果与数据库结果一致。本研究结果表明，CNOT6、CNOT10和CNOT11作为转录调节因子，可能在HCC的发生发展中起重要作用，并可作为HCC诊断和预后的生物学标志物。
