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ASPM is a Novel Candidate Gene Associated with Colorectal Cancer Cell Growth
DNA and Cell Biology ( IF 3.1 ) Pub Date : 2021-07-15 , DOI: 10.1089/dna.2020.6457
Qian Yang 1, 2, 3 , Mingming Qi 1, 2, 3 , Yongyu Chen 1, 2 , Shan Tian 1 , Fei Liao 1 , Weiguo Dong 1, 2
Affiliation  

Colorectal cancer (CRC) is one of the most prevalent diseases worldwide; however, the molecular mechanisms involved in CRC remain unclear. Thus, we aimed to explore a novel biomarker for CRC. In this study, we screened 361 differentially expressed genes; 152 downregulated genes; and 209 upregulated genes) through analysis of the GSE44861, GSE110223, GSE110224, and GSE113513 CRC datasets. Next, ASPM, CCNA2, CCNB1, CEP55, KIF20A, MAD2L1, MELK, RRM2, TOP2A, TPX2, TRIP13, and TTK were identified as hub genes associated with the cell cycle in CRC through comprehensive bioinformatics analysis using the Cytoscape and Metascape software, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases. Furthermore, ASPM mRNA expression in CRC tissues was verified in Oncomine, The Cancer Genome Atlas and our data, and ASPM was found to be significantly upregulated in CRC tissues compared with that in the noncancer colon tissues. Functionally, we showed that overexpression of ASPM significantly promoted the proliferation and inhibited apoptosis; silencing of ASPM suppressed the proliferation of CRC cells by affecting the cell cycle G1/S transition by reducing cyclin E1 expression, and inducing apoptosis. Overall, our findings indicated that ASPM plays a crucial role in the regulation of CRC cell proliferation, and ASPM is a potential candidate diagnostic tool and therapeutic target for CRC.

中文翻译:

ASPM 是一种与结直肠癌细胞生长相关的新型候选基因

结直肠癌 (CRC) 是全球最流行的疾病之一。然而,CRC 所涉及的分子机制仍不清楚。因此,我们旨在探索一种新的 CRC 生物标志物。在本研究中,我们筛选了 361 个差异表达基因;152个下调基因;和 209 个上调基因)通过分析 GSE44861、GSE110223、GSE110224 和 GSE113513 CRC 数据集。接下来,ASPMCCNA2、CCNB1CEP55KIF20AMAD2L1MELKRRM2TOP2ATPX2TRIP13TTK通过使用 Cytoscape 和 Metascape 软件、注释、可视化和集成发现数据库 (DAVID) 以及 Oncomine 和基因表达分析交互式分析 2 (GEPIA2) 进行全面的生物信息学分析,确定了与 CRC 中细胞周期相关的中枢基因数据库。此外,结直肠癌组织中的ASPM mRNA 表达在 Oncomine、癌症基因组图谱和我们的数据中得到验证,并且发现与非癌结肠组织相比,结直肠癌组织中的ASPM显着上调。在功能上,我们发现ASPM的过表达显着促进增殖并抑制细胞凋亡;沉默ASPM通过降低细胞周期蛋白 E1 表达和诱导细胞凋亡来影响细胞周期 G1/S 转换,从而抑制 CRC 细胞的增殖。总体而言,我们的研究结果表明,ASPM在调节 CRC 细胞增殖中起着至关重要的作用,ASPM是CRC的潜在候选诊断工具和治疗靶点。
更新日期:2021-07-20
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