Identification of potential therapeutic targets for colorectal cancer by bioinformatics analysis

Yan, Ming; Song, Man; Bai, Rong; Cheng, Shi Yuan; Yan, Wenmao

doi:10.3892/ol.2016.5328

Cited by 19 publications

(15 citation statements)

References 49 publications

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“…Involved in cell cycle, for example, CDK1 was identified as upregulated (FDR=3.52e-10), which was reported as upregulated in CRC tissues and cell lines [23]. For another example, the increased expression of CCNB1 was observed in CRC as previously reported [24,25], which was also identified as an upregulated gene in CRC in this study (FDR=1.49e-09). On the other hand, functional enrichment analysis of the 1767 downregulated genes showed the close relation with cGMP-PKG signaling pathway (FDR=2.32e-09), calcium signaling pathway (FDR=2.91e-09), circadian entrainment (FDR=7.09e-09), vascular smooth muscle contraction (FDR=2.02e-08), ECM-receptor interaction (FDR=1.94e-06), and focal adhesion (FDR=6.97e-06) etc.…”

Section: Resultssupporting

confidence: 83%

Impact of Colon-Specific DNA Methylation-Regulated Gene Modules on Colorectal Cancer Patient Survival

Jiang

Chen

et al. 2019

Med Sci Monit

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Background Colorectal cancer (CRC) is the second most commonly diagnosed cancer in females and the third in males worldwide. Although existing evidence explained some critical functions of the single genetic abnormality in the pathogenesis of CRC, the function of interactors involved in the colon-specific regulatory network, especially DNA methylation regulated network is still poorly understood. Material/Methods In this work, matched gene expression and DNA methylation samples of CRC patients were retrieved. Differential gene expression and methylation analyses were performed. In addition, gene expression and DNA methylation were integrated into a colon-specific regulatory gene network, detecting the epigenetically regulated gene modules which drive CRC through an underlying epigenetic mechanism. Finally, the colon-specific DNA methylation-regulated gene modules were validated using an independent set of CRC patients. Results Differential gene expression analysis demonstrated the upregulation of the cell cycle and DNA replication and downregulation of cGMP-PKG signaling pathway and calcium signaling pathway in CRC. Differentially methylated regions (DMRs) showed the different levels of methylation in promoters, CpG islands, and genes in CRC. In addition, gene expression and DNA methylation were integrated into a colon-specific regulatory gene network, detecting 8 epigenetically regulated gene modules which drive CRC through an underlying epigenetic mechanism. Interestingly, 2 of the colon-specific DNA methylation-regulated gene modules showed a significant predictive ability for the survival of an independent set of CRC patients. Conclusions The results of this study could open a new era and aid the development of novel therapeutic targets for the treatment of CRC patient.

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Section: Resultssupporting

confidence: 83%

Impact of Colon-Specific DNA Methylation-Regulated Gene Modules on Colorectal Cancer Patient Survival

Jiang

Chen

et al. 2019

Med Sci Monit

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“…Iwaya et al identified DEGs between CRC patients and normal colon epithelium (12). Yan et al also identified potential biomarkers for the prognosis and prevention of CRC (13). Bioinformatic methods owing to their efficiency in dealing with high-throughput data are currently now in use, but the most representative DEGs or pathways still need to be identified.…”

Section: Introductionmentioning

confidence: 99%

Identification of key tumorigenesis‑related genes and their microRNAs in colon cancer

et al. 2018

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Colorectal cancer (CRC) is one of the most common malignant tumors and its development involves multi-gene driven processes that affect the digestive system. The objective of this study was to identify tumorigenesis-associated gene signatures using microarray expression profiling data. The gene expression profiling of GSE39582, a dataset containing 566 colon cancer samples and 19 non-tumoral colorectal mucosae was downloaded from Gene Expression Omnibus (GEO) database. A total of 439 differentially expressed genes (DEGs) were extracted by GEO2R. Many of these DEGs were cancer-related, involved in the regulation of cell proliferation, extracellular matrix (ECM)-receptor interaction and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway according to the results of pathway enrichment analysis in Database for Annotation, Visualization and Integrated Discovery (DAVID). Then, 10 genes were predicted to play an important role in the development of CRC. Transient receptor potential cation channel, subfamily M, and member 6 (TRPM6), a member of 10 hub genes, was confirmed to be downregulated in 16 (80%) of 20 colon cancer tissues using quantitative polymerase chain reaction (qPCR) technology. Furthermore, high expression of TRPM6 was indicative of a prolonged overall survival (OS) in CRC patients through the analysis of GSE39582. Hsa-let-7g and hsa-let-7f-1 were believed to be the regulatory miRNAs of TRPM6 by TCGA and miRanda database. In conclusion, this study may play a critical role in promoting the discovery of potential targets for diagnosis, treatment and prognosis of CRC.

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“…Although the detection approaches has been advanced, the incidence of human colorectal cancer with high morbidity and mortality rate remains high [ 1 ]. The annual incidence of human colorectal cancer is estimated to be ~1 million, with ~500,000 mortalities [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Anticancer activity of calyx of Diospyros kaki Thunb. through downregulation of cyclin D1 via inducing proteasomal degradation and transcriptional inhibition in human colorectal cancer cells

Park¹,

Park²,

Song³

et al. 2017

BMC Complement Altern Med

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BackgroundAlthough it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells.MethodsAnti-cell proliferative effect of 70% ethanol extracts from the calyx of Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the expression of cyclin D1 in the protein and mRNA level was evaluated by Western blot and RT-PCR, respectively.ResultsDKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity.ConclusionsOur results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer.

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Identification of potential therapeutic targets for colorectal cancer by bioinformatics analysis

Cited by 19 publications

References 49 publications

Impact of Colon-Specific DNA Methylation-Regulated Gene Modules on Colorectal Cancer Patient Survival

Impact of Colon-Specific DNA Methylation-Regulated Gene Modules on Colorectal Cancer Patient Survival

Identification of key tumorigenesis‑related genes and their microRNAs in colon cancer

Anticancer activity of calyx of Diospyros kaki Thunb. through downregulation of cyclin D1 via inducing proteasomal degradation and transcriptional inhibition in human colorectal cancer cells

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