CTPS1 inhibition suppresses proliferation and migration in colorectal cancer cells

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.

Keywords: CTPS1; Colorectal cancer (CRC); biomarker; cell cycle; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Tumor Suppressor Protein p53
  • GTSE1 protein, human
  • Microtubule-Associated Proteins

Grants and funding

Supported by Science and technology projects in Cheng guan District of Lanzhou City(2014-4-4) and Lanzhou city science and technology development guidance plan project (No. 2019-ZD-71).