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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Gene Expression Alterations and Molecular Analysis of CHEK1 in Solid Tumors
Adewale Oluwaseun Fadaka1, Olalekan Olanrewaju Bakare1, Nicole Remaliah Samantha Sibuyi2
1Bioinformatics research group, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa.
Abstract:
Alterations in the Checkpoint kinase (CHEK1) gene, its regulation, and the possible clinical outcomes in human solid tumors have not been previously examined. Therefore, the present study was carried out to evaluate the expression of CHEK1 in solid tumors as well as the mechanism by which it can be regulated through non-coding RNAs. The expression of CHEK1 was investigated using Oncomine analysis. cBioPortal, Kaplan-Meier Plotter, and PrognoScan were performed to identify the prognostic roles of this gene in solid tumors. The copy number alteration, mutation, interactive analysis, and visualization of the altered networks were performed by cBioPortal. The molecular binding analysis was carried out by Schrodinger suite, PATCHDOCK, and discovery studio visualizer. The study demonstrated that the CHEK1 gene was differentially expressed in four different cancers, and that reduced CHEK1 mRNA expression is an unfavorable prognostic factor for patients with gastric and colorectal cancer. The molecular docking results showed that the CHEK1 gene can be regulated by microRNAs (miR-195-5p) due to the number of stable hydrogen atoms observed within the distance of 2.0 Å and the favorable amino acids (Ala221, Ile353, Ile365, Ile756, Val797, Val70, Val154, Ile159, Val347, Tyr804, Phe811, Tyr815, and Phe156) identified in the binding pocket of the argonaute protein. Due to the possibility of CHEK1's involvement in solid tumors, it may potentially be a target for therapeutic intervention in cancer. Further studies into the interaction between CHEK1 and other co-expressed genes may give further insight into other modes of regulation of this gene in cancer patients.
Insights
Checkpoint kinase 1 (CHEK1) gene alterations and regulation in solid tumors were examined. Reduced CHEK1 mRNA expression indicates a poor prognosis in gastric and colorectal cancers, suggesting CHEK1 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- The role of Checkpoint kinase 1 (CHEK1) gene alterations and regulation in human solid tumors remains largely unexplored.
- Understanding CHEK1's expression patterns and regulatory mechanisms is crucial for identifying potential cancer biomarkers and therapeutic targets.
Purpose of the Study:
- To investigate the expression of the CHEK1 gene in various solid tumors.
- To elucidate the regulatory mechanisms of CHEK1, particularly focusing on non-coding RNAs.
- To evaluate the prognostic significance of CHEK1 in human solid tumors.
Main Methods:
- Gene expression analysis using Oncomine.
- Prognostic role assessment via cBioPortal, Kaplan-Meier Plotter, and PrognoScan.
- Network analysis and molecular docking using cBioPortal, Schrodinger suite, PATCHDOCK, and discovery studio visualizer.
Main Results:
- CHEK1 was found to be differentially expressed in four cancer types.
- Lower CHEK1 mRNA expression correlated with unfavorable outcomes in gastric and colorectal cancer patients.
- Molecular docking revealed potential regulation of CHEK1 by microRNA (miR-195-5p) through stable binding interactions.
Conclusions:
- CHEK1 exhibits differential expression in solid tumors, with reduced levels indicating a poor prognosis in specific cancers like gastric and colorectal.
- MicroRNA-mediated regulation of CHEK1 is plausible, highlighting miR-195-5p as a potential regulator.
- CHEK1 represents a promising therapeutic target for cancer treatment, warranting further investigation into its regulatory networks.
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