Abstract：
Glioma is the most common malignant brain tumor in the central nervous system with the poor prognosis of patients. The CNOT7 (CCR4-NOT Transcription Complex Subunit 7) is an important functional subunit of CCR4-NOT protein complex that has not been reported in glioma. In this study, we aimed to explore the function of CNOT7 in glioma. The TCGA (The Cancer Genome Atlas) and CGGA (Chinese Glioma Genome Atlas) databases were used for investigating the expression and survival condition of CNOT7 in glioma. The cellular function experiments of qRT-PCR, CCK-8 assays, wound healing assays, and Transwell assays were conducted to verify the function of knockdown CNOT7 in the glioma cell lines DBTRG and U251. Enrichment analysis was used to explore the molecular mechanism of CONT7 in glioma. What is more, the upstream regulation transcription factors of CNOT7 were analyzed based on the ChIP-Atlas and cBioportal (provisional) databases, and verified by the qRT-PCR and luciferase reporter assay. The CNOT7 was highly expressed in glioma and presented the poorer prognosis. The knockdown of CNOT7 inhibited the proliferation, migration, and invasion of glioma cell line, compared to control group. The enrichment analysis revealed that the CNOT7 participated in the development of glioma via G2M checkpoint, E2F targets, IL6-JAK-STAT3, and TNF-α signaling pathways via NF-κB. Besides, it was found that the HDAC2 (Human histone deacetylase-2) contributes to increased CNOT7 expression in glioma. The high-expressed CNOT7 is an oncogene with poor prognosis and participate the progression of glioma.
摘要：
胶质瘤是中枢神经系统中最常见的恶性脑肿瘤，患者预后较差。CNOT7（CCR4-NOT转录复合物亚基7）是CCR4-NOT蛋白复合物的重要功能亚基，在神经胶质瘤中尚未报道。在这项研究中,我们旨在探讨CNOT7在胶质瘤中的作用。使用TCGA（癌症基因组图谱）和CGGA（中国胶质瘤基因组图谱）数据库研究CNOT7在胶质瘤中的表达和生存状况。qRT-PCR的细胞功能实验,CCK-8测定，伤口愈合试验，进行了Transwell实验以验证敲低CNOT7在神经胶质瘤细胞系DBTRG和U251中的功能。富集分析探讨CONT7在胶质瘤中的分子机制。更重要的是，基于ChIP-Atlas和cBioportal（临时）数据库分析了CNOT7的上游调控转录因子，并通过qRT-PCR和荧光素酶报告基因测定进行验证。CNOT7在神经胶质瘤中高表达，预后较差。CNOT7的敲除抑制增殖，迁移,和神经胶质瘤细胞系的侵袭，与对照组相比。富集分析表明，CNOT7通过G2M检查点参与了神经胶质瘤的发展，E2F目标,IL6-JAK-STAT3和通过NF-κB的TNF-α信号通路。此外,发现HDAC2（人类组蛋白脱乙酰酶-2）有助于神经胶质瘤中CNOT7表达的增加。高表达的CNOT7是预后不良的癌基因，参与了胶质瘤的进展。
