Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer

Miteva, Lyuba; Stanilov, Noyko; Cirovski, G.; Stanilova, Spaska

doi:10.1007/s12307-017-0198-5

Cited by 14 publications

(13 citation statements)

References 28 publications

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“…Among these crucial genes, CDK1, CCNB1, CCNA2, IL6 and NOTCH1 have been reported to be associated with CRC proliferation and progression (29)(30)(31)(32)(33). In particular, CDK1 is a key regulator of the G 2 /M checkpoint and is considered to be a possible target for cancer treatment (30).…”

Section: Discussionmentioning

confidence: 99%

“…IL6, a proinflammatory cytokine secreted by immune cells, may mediate immune and CRC cell cross-talk via miR-21 and miR-29b to produce an inflammatory microenvironment sufficient for promoting metastatic growth (32). In addition, Miteva et al (33) have reported that overexpression of IL6 promotes the migration and invasion of CRC cells, and upregulation of IL6 may be a transcriptional profile hallmark of colorectal metastases. Lv et al (34) have revealed that MYC regulates CRC progression, and that its overexpression enhances tumour metastasis and chemotherapy resistance in CRC.…”

Section: Discussionmentioning

confidence: 99%

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Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis

Liu

Qiao

et al. 2020

Oncol Lett

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Colorectal cancer (CRC) is a prevalent malignant tumour type arising from the colon and rectum. The present study aimed to explore the molecular mechanisms of the development and progression of CRC. Initially, differentially expressed genes (DEGs) between CRC tissues and corresponding non-cancerous tissues were obtained by analysing the GSE15781 microarray dataset. The Database for Annotation, Visualization and Integrated Discovery was then utilized for functional and pathway enrichment analysis of the DEGs. Subsequently, a protein-protein interaction (PPI) network was created using the Search Tool for the Retrieval of Interacting Genes and Proteins database and visualized by Cytoscape software. Furthermore, CytoNCA, a Cytoscape plugin, was used for centrality analysis of the PPI network to identify crucial genes. Finally, UALCAN was employed to validate the expression of the crucial genes and to estimate their effect on the survival of patients with colon cancer by Kaplan-Meier curves and log-rank tests. A total of 1,085 DEGs, including 496 upregulated and 589 downregulated genes, were screened out. The DEGs identified were enriched in various pathways, including 'metabolic pathway', 'cell cycle', 'DNA replication', 'nitrogen metabolism', 'p53 signalling' and 'fatty acid degradation'. PPI network analysis suggested that interleukin-6, MYC, NOTCH1, inhibin subunit βA (INHBA), CDK1, cyclin (CCN)B1 and CCNA2 were crucial genes, and their expression levels were markedly upregulated. Survival analysis suggested that upregulated INHBA significantly decreased the survival probability of patients with CRC. Conversely, upregulation of CCNB1 and CCNA2 expression levels were associated with increased survival probabalities. The identified DEGs, particularly the crucial genes, may enhance the current understanding of the genesis and progression of CRC, and certain genes, including INHBA, CCNB1 and CCNA2, may be candidate diagnostic and prognostic markers, as well as targets for the treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis

Liu

Qiao

et al. 2020

Oncol Lett

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“…Tumor suppressive functions are mainly manifested by the inhibition of cell proliferation with the simultaneous induction of programmed cell death in early carcinogenesis. In normal epithelial cells, TGF-β1 signalling through the canonical pathway inhibits proliferation by inducing the production of cyclin-dependent kinase inhibitors and repressing the proto-oncogene c-myc [ 22 , 23 , 7 ]. Additionally, the anti-inflammatory activity of this cytokine in the mucosa enhances anti-tumor activities by suppressing tumor-elicited inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…The predesigned inventoried TaqMan gene expression assays for TGFB1 (Hs00998133_m1) and for the endogenous controls/reference genes GAPDH (Hs02758991_g1) and eukaryotic 18S ribosomal RNA (Hs99999901_s1) were purchased from Thermo Fisher Scientific. The procedure is described in detail in our previous study [ 7 ].…”

Section: Methodsmentioning

confidence: 99%

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Transforming growth factor-β1 gene promoter -509C/T polymorphism in association with expression affects colorectal cancer development and depends on gender

et al. 2018

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It is widely known that sporadic colorectal cancer (CRC) is age-related diseases with higher incidence rate among men. Transforming growth factor-β1 (TGF-β1) is a major immune regulatory cytokine with a great impact and dual role in gastrointestinal carcinogenesis. In this context, the aim of the study was to explore the role of circulating TGF-β1 and the -509C/T functional promoter polymorphism (rs1800469) within the TGF-β1 gene (TGFB1) in the susceptibility, progression, and prognosis of CRC among Bulgarian male and female patients. Patients with sporadic CRC and healthy controls were genotyped by polymerase-chain reaction–restriction fragment length polymorphism. Serum TGF-β1 levels before and after curative surgery were determined by ELISA. Total RNA was extracted from paired tumor, normal mucosa and distant metastasis samples and was used for quantitative detection of TGFB1 mRNA by TaqMan qPCR.We observed that TGF-β1 serum levels depend on the -509C/T genotype in combination with gender. TGF-β1 serum levels in CRC patients were decreased compared to controls, but statistical significance was reached only for men. In the stratified analysis by gender and genotype, a significant association was found for the CC genotype. Overall, our results indicate that the -509C allele increased the cancer risk, particularly for advanced stages (OR = 1.477; p = 0.029). The results from the relative mRNA quantification showed a significant upregulation of TGFB1 in distant metastases compared to primary tumor tissues and higher TGFB1 mRNA levels in men (RQ = 4.959; p = 0.022). In conclusion, we present data that diminished circulating TGF-β1 due to the CC genotype could be a possible risk factor for tumor susceptibility and progression. This association is more pronounced in males than in females. Colorectal cancer tissue expression of TGFB1 gene mRNA correlates with tumor progression and metastasis.

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Low serum level of 25‐OH vitamin D relates to Th17 and treg changes in colorectal cancer patients

Chen

Jin

2022

Immunity Inflam & Disease

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Background: Serum 25-hydroxyvitamin D [25(OH)D] level alters in colorectal cancer (CRC) development. Regulatory T (Treg) cells and T-helper type 17 (Th17) cells are involved in immune response. Th17-mediated proinflammatory responses contribute to tumorigenesis, and Treg plays different roles in different periods of CRC. Vitamin D deficiency is associated with significant variations in peripheral immune cells. This study investigated the relationship between Th17 and Treg cells and 25(OH)D level in CRC. Methods: Ninety-five CRC patients were included, as well as 80 healthy controls during the same period at the Affiliated Hospital of Jiangnan University. 25(OH)D level was analyzed through electrochemiluminescence (ECLIA). Th17 and Treg levels were evaluated through flow cytometry. Serum levels of interleukin (IL)-10, IL-17, IL-23, and transforming growth factor-β (TGF-β), were analyzed through commercial enzyme-linked immunoassay (ELISA) kits. Results: 25(OH)D levels were downregulated in the serum of CRC patients. Decreased 25(OH)D level contributed to CRC pathogenesis. Decreased 25(OH) D level in CRC correlated with increased Treg and Th17 cell ratios and TGF-β1, IL-10, IL-17, and IL-23 levels in peripheral blood. Conclusion: Decreased 25(OH)D level in the serum of CRC patients had negative correlation with Treg and Th17 ratios and relative cytokines levels.

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Upregulation of Treg-Related Genes in Addition with IL6 Showed the Significant Role for the Distant Metastasis in Colorectal Cancer

Cited by 14 publications

References 28 publications

Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis

Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis

Transforming growth factor-β1 gene promoter -509C/T polymorphism in association with expression affects colorectal cancer development and depends on gender

Low serum level of 25‐OH vitamin D relates to Th17 and treg changes in colorectal cancer patients

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