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CTPS1 抑制可抑制结直肠癌细胞的增殖和迁移。

CTPS1 inhibition suppresses proliferation and migration in colorectal cancer cells.

机构信息

Department of General Surgery, Hepatic-biliary-pancreatic Institute, Lanzhou University Second Hospital, Lanzhou, China.

Department of Hematology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.

出版信息

Cell Cycle. 2022 Dec;21(24):2563-2574. doi: 10.1080/15384101.2022.2105084. Epub 2022 Aug 1.

Abstract

Colorectal cancer (CRC) is now the third most prevalent tumor and one of the deadliest cancers worldwide, with an increasing prevalence every year. Therefore, we urgently need to understand the mechanisms regulating the progression of colorectal cancer and find potential diagnostic biomarkers. In this study, we performed an analysis using the TCGA and GEO databases to find a molecular biomarker for the diagnosis of CRC, namely CTPS1. The results of this analysis revealed that CTPS1 could promote tumor proliferation and metastasis. Furthermore, bioinformatics analysis revealed that CTPS1 promoted CRC progression through cell cycle and p53 pathways. Further investigation demonstrated that CTPS1 might be involved in the regulation of CCNB1, RRM2, GTSE1, CDK2 and CHEK2 genes. Moreover, PCR confirmed that CTPS1 regulated GTSE1 and CDK2 molecules. Then, western blot was used to verify that CTPS1 promoted the expression of GTSE1 and CDK2 by inhibiting the expression of p53. In summary, we identified an important diagnostic biomarker for CRC, namely CTPS1, and its importance was validated at the cellular level. These results suggest that CTPS1 could serve as a candidate biomarker for CRC and CTPS1 inhibitors may be a potential treatment for CRC.

摘要

结直肠癌(CRC)现已成为全球第三大常见肿瘤和最致命癌症之一,且其发病率呈逐年上升趋势。因此,我们迫切需要了解调控结直肠癌进展的机制,并寻找潜在的诊断生物标志物。在本研究中,我们通过 TCGA 和 GEO 数据库进行分析,以寻找用于 CRC 诊断的分子生物标志物,即 CTPS1。该分析的结果表明 CTPS1 可促进肿瘤增殖和转移。此外,生物信息学分析表明 CTPS1 通过细胞周期和 p53 途径促进 CRC 进展。进一步的研究表明,CTPS1 可能参与调控 CCNB1、RRM2、GTSE1、CDK2 和 CHEK2 基因。此外,PCR 证实 CTPS1 通过抑制 p53 的表达来调控 GTSE1 和 CDK2 分子。然后,使用 Western blot 验证 CTPS1 通过抑制 p53 的表达促进 GTSE1 和 CDK2 的表达。总之,我们确定了用于 CRC 的重要诊断生物标志物 CTPS1,并在细胞水平上验证了其重要性。这些结果表明 CTPS1 可以作为 CRC 的候选生物标志物,CTPS1 抑制剂可能是 CRC 的潜在治疗方法。

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