Checkpoint kinase 1 in colorectal cancer: Upregulation of expression and promotion of cell proliferation

Abstract

BACKGROUND

Colorectal cancer (CRC) is a prevalent malignant tumor characterized by a high mortality rate, with significant challenges persisting in the identification and management of its metastatic stage. The role of checkpoint kinase 1 (CHEK1), a cell cycle checkpoint kinase, in CRC has not been fully clarified. We hypothesize that the upregulation of CHEK1 may enhance the proliferation of CRC cells, indicating its potential as a novel therapeutic target for CRC therapy.

AIM

To investigate the expression and function of CHEK1 in CRC, this study utilizes single-cell RNA sequencing and tissue microarray data.

METHODS

Single-cell RNA sequencing technology was employed to analyze CRC cells from the GSE144735 dataset, and immunohistochemistry was conducted to confirm the expression of CHEK1 in CRC and adjacent tissues. We also integrated mRNA expression data from multiple public databases to assess global CHEK1 expression in CRC. Molecular docking experiments were performed to explore the interaction between CHEK1 and the potential drug nitidine chloride (NC), as well as to investigate the influence of CHEK1 on CRC cell proliferation.

RESULTS

We found comparatively elevated CHEK1 expression in the malignant epithelial cells of CRC, with marked upregulation of its mRNA levels in CRC tissues. Immunohistochemical analysis further confirmed the high expression of CHEK1 in CRC tissues, and the receiver operating characteristic curve demonstrated high accuracy (area under the curve = 0.964) for CHEK1 as a biomarker. Analysis of global datasets indicated a statistically significant overexpression of CHEK1 in CRC (standard mean difference = 1.81, P < 0.01), with summary receiver operating characteristic analysis yielding sensitivity and specificity values of 0.83 and 0.88, respectively. Molecular docking studies indicated that NC specifically targeted CHEK1, while clustered regularly interspaced short palindromic repeats knockout experiments demonstrated that CHEK1 promoted CRC cell proliferation.

CONCLUSION

Upregulation of CHEK1 promotes CRC cell proliferation. However, the dataset's diversity is limited, requiring further investigation into its specific mechanisms.

Keywords: Colorectal cancer; Checkpoint kinase 1; Single-cell sequencing; Immunohistochemistry; Molecular docking

Core Tip: This study demonstrates that checkpoint kinase 1 (CHEK1) is comparatively overexpressed in colorectal cancer (CRC) and is closely associated with tumor proliferation. Based on single-cell RNA sequencing and immunohistochemistry, the findings highlight CHEK1’s potential as a novel biomarker and therapeutic target in CRC. Furthermore, the research uncovers nitidine chloride as a specific CHEK1 inhibitor, suggesting promising avenues for targeted therapies to improve patient outcomes. These insights underscore the clinical relevance of CHEK1 in CRC management and the need for further exploration of its mechanistic roles.