Oncogenic Gene CNOT7 Promotes Progression and Induces Poor Prognosis of Glioma.

IF 2.5 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Molecular Biotechnology Pub Date : 2025-07-01 Epub Date: 2024-07-10 DOI:10.1007/s12033-024-01223-5
Feng Lu, Xiulong Jiang, Kun Lin, Pengfeng Zheng, Shizhong Wu, Guangming Zeng, De Wei
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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.

Abstract Image

致癌基因 CNOT7 促进胶质瘤进展并诱导不良预后
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 蛋白复合物的一个重要功能亚基,但在胶质瘤中尚未见报道。本研究旨在探讨 CNOT7 在胶质瘤中的功能。研究使用了TCGA(The Cancer Genome Atlas)和CGGA(Chinese Glioma Genome Atlas)数据库来研究CNOT7在胶质瘤中的表达和生存状况。通过qRT-PCR、CCK-8检测、伤口愈合检测和Transwell检测等细胞功能实验,验证了敲除CNOT7在胶质瘤细胞株DBTRG和U251中的功能。利用富集分析探讨了CONT7在胶质瘤中的分子机制。此外,还基于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和荧光素酶报告实验进行了验证。CNOT7在胶质瘤中高表达,预后较差。与对照组相比,敲除 CNOT7 可抑制胶质瘤细胞系的增殖、迁移和侵袭。富集分析表明,CNOT7通过G2M检查点、E2F靶点、IL6-JAK-STAT3和TNF-α信号通路经NF-κB参与胶质瘤的发展。此外,研究还发现,HDAC2(人类组蛋白去乙酰化酶-2)是胶质瘤中 CNOT7 表达增加的原因之一。高表达的CNOT7是一种预后不良的癌基因,会参与胶质瘤的进展。
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来源期刊
Molecular Biotechnology
Molecular Biotechnology 医学-生化与分子生物学
CiteScore
4.10
自引率
3.80%
发文量
165
审稿时长
6 months
期刊介绍: Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.
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