Fadaka Adewale Oluwaseun, Bakare Olalekan Olanrewaju, Sibuyi Nicole Remaliah Samantha, Klein Ashwil
Bioinformatics research group, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa.
Department of Science and Technology/Mintek Nanotechnology Innovation Centre, Biolabels Node, Department of Biotechnology, Faculty of Natural Sciences, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa.
Cancers (Basel). 2020 Mar 12;12(3):662. doi: 10.3390/cancers12030662.
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.
此前尚未研究过检查点激酶（CHEK1）基因的改变、其调控以及在人类实体瘤中的可能临床结果。因此，本研究旨在评估CHEK1在实体瘤中的表达以及通过非编码RNA对其进行调控的机制。使用Oncomine分析研究CHEK1的表达。通过cBioPortal、Kaplan-Meier Plotter和PrognoScan来确定该基因在实体瘤中的预后作用。由cBioPortal进行拷贝数改变、突变、交互分析以及对改变网络的可视化。通过Schrodinger套件、PATCHDOCK和Discovery Studio可视化器进行分子结合分析。该研究表明，CHEK1基因在四种不同癌症中差异表达，并且CHEK1 mRNA表达降低对胃癌和结直肠癌患者来说是一个不利的预后因素。分子对接结果显示，由于在距离2.0 Å内观察到的稳定氢原子数量以及在AGO蛋白结合口袋中鉴定出的有利氨基酸（Ala221、Ile353、Ile365、Ile756、Val797、Val70、Val154、Ile159、Val347、Tyr804、Phe811、Tyr815和Phe156），CHEK1基因可被微小RNA（miR-195-5p）调控。由于CHEK1可能参与实体瘤，它可能潜在地成为癌症治疗干预的靶点。对CHEK1与其他共表达基因之间相互作用的进一步研究可能会更深入地了解该基因在癌症患者中的其他调控模式。
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