Screening and regulatory network analysis of survival-related genes of patients with colorectal cancer

Lü, Qing; Ding, Yan‐Qing

doi:10.1007/s11427-014-4650-1

Cited by 10 publications

(8 citation statements)

References 13 publications

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“…NF-κB signaling pathway hyperactivation plays critical roles in different malignant progression-associated processes, including tumorigenesis, angiogenesis, invasion, and metastasis 12 – 16 . Our previous bioinformatics analysis of several public gene expression profiles showed that STX2 upregulation was correlated with a poor prognosis for CRC patients and could increase the activity of the NF-κB signaling pathway 17 . However, the molecular mechanisms through which STX2 regulates NF-κB signaling pathway activation remain unclear.…”

Section: Introductionmentioning

confidence: 99%

STX2 promotes colorectal cancer metastasis through a positive feedback loop that activates the NF-κB pathway

Wang

Jiao

et al. 2018

Cell Death Dis

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Metastatic progression is the main contributor to the poor prognosis of colorectal cancer (CRC). Thus, identifying the determinants of CRC metastasis will be of great significance. Based on our previous bioinformatics analysis, Syntaxin2 (STX2) may be upregulated and correlated with the poor prognosis of CRC patients. In this study, we found that STX2 expression was associated with CRC invasion and metastasis and poor patient survival. Gain- and loss-of-function analyses demonstrated that STX2 functioned as a key oncogene by promoting CRC invasion and metastasis. Mechanistically, STX2 selectively interacted with tumor necrosis factor receptor-associated factor 6 (TRAF6) and activated the nuclear transcription factor-κB (NF-κB) signaling pathway. Furthermore, chromatin immunoprecipitation (ChIP) analysis revealed that NF-κB directly bound to the STX2 promoter and drove STX2 transcription. Therefore, STX2 activated the NF-κB pathway, and in turn, NF-κB increased STX2 expression, forming a positive signaling loop that eventually promoted CRC metastasis. Collectively, our results reveal STX2 as a crucial modulator of the aggressive CRC phenotype and highlight STX2 as a potential prognostic biomarker and therapeutic target for combating CRC metastasis.

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Section: Introductionmentioning

confidence: 99%

STX2 promotes colorectal cancer metastasis through a positive feedback loop that activates the NF-κB pathway

Wang

Jiao

et al. 2018

Cell Death Dis

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“…KLK6 mRNA expression is elevated in malignant colorectal tissues compared with non-malignant ones and correlates with serosal invasion, liver metastasis, advanced Duke's stage, and a poor prognosis [17], [18], [19]. The bioinformatics analysis of expression data from a cohort of colorectal cancer patients, identified the KLK6 gene as one of the top six up-regulated genes associated with the survival of colorectal cancer patients through metastasis related signaling pathways [20]. The mechanism of regulation of KLK6 expression in colon cancer is not fully investigated.…”

Section: Introductionmentioning

confidence: 99%

Specific microRNA–mRNA Regulatory Network of Colon Cancer Invasion Mediated by Tissue Kallikrein–Related Peptidase 6

et al. 2017

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Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer. KLK6 suppression resulted in decreased cells invasion in vitro with a minimal effect on the cell growth and viability. In vivo, animals with orthotopic colon tumors deficient in KLK6 expression had the statistically significant increase in survival rates (P = .005) and decrease in incidence of distant metastases. We further performed the integrated miRNA and messenger RNA (mRNA) expression profiling to identify functional miRNA-mRNA interactions associated with KLK6-mediated invasiveness of colon cancer.Through bioinformatics analysis we identified and functionally validated the top two up-regulated miRNAs, miR-182 and miR-203, and one down-regulated miRNA, miRNA-181d, and their seven mRNA effectors. The established miRNA-mRNA interactions modulate cellular proliferation, differentiation and epithelial–mesenchymal transition (EMT) in KLK6-expressing colon cancer cells via the TGF-β signaling pathway and RAS-related GTP-binding proteins. We confirmed the potential tumor suppressive properties of miR-181d and miR-203 in KLK6-expressing HCT116 cells using Matrigel invasion assay. Our data provide experimental evidence that KLK6 controls metastasis formation in colon cancer via specific downstream network of miRNA-mRNA effectors.

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“…Therefore, the effect of the gene is not affected by lifestyle. CREB5 gene affects the survival of patients by regulating colorectal cancer metastasis-associated signaling pathways [31]. Moreover, the additive effect of another gene LMNTD1 also did not significantly changed in the cofactor models.…”

Section: Plos Onementioning

confidence: 86%

Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population

Khatun

Monir

et al. 2021

PLoS ONE

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Body surface area (BSA) is an important trait used for many clinical purposes. People’s BSA may vary due to genetic background, race, and different lifestyle factors (such as walking, exercise, reading, smoking, transportation, etc.). GWAS of BSA was conducted on 5,324 subjects of four ethnic populations of European-American, African-American, Hispanic-American, and Chinese-American from the Multi-Ethnic Study of Atherocloris (MESA) data using unconditional and conditional full genetic models. In this study, fifteen SNPs were identified (Experiment-wise PEW < 1×10−5) using unconditional full genetic model, of which thirteen SNPs had individual genetic effects and seven SNPs were involved in four pairs of epistasis interactions. Seven single SNPs and eight pairs of epistasis SNPs were additionally identified using exercise, smoking, and transportation cofactor-conditional models. By comparing association analysis results from unconditional and cofactor conditional models, we observed three different scenarios: (i) genetic effects of several SNPs did not affected by cofactors, e.g., additive effect of gene CREB5 (a≙ –0.013 for T/T and 0.013 for G/G, −Log10 PEW = 8.240) did not change in the cofactor models; (ii) genetic effects of several SNPs affected by cofactors, e.g., the genetic additive effect (a≙ 0.012 for A/A and –0.012 for G/G, −Log10 PEW = 7.185) of SNP of the gene GRIN2A was not significant in transportation cofactor model; and (iii) genetic effects of several SNPs suppressed by cofactors, e.g., additive (a≙ –0.018 for G/G and 0.018 for C/C, −Log10 PEW = 19.737) and dominance (d≙ –0.038 for G/C, −Log10 PEW = 27.734) effects of SNP of gene ERBB4 was identified using only transportation cofactor model. Gene ontology analysis showed that several genes are related to the metabolic pathway of calcium compounds, coronary artery disease, type-2 Diabetes, Alzheimer disease, childhood obesity, sleeping duration, Parkinson disease, and cancer. This study revealed that lifestyle cofactors could contribute, suppress, increase or decrease the genetic effects of BSA associated genes.

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Screening and regulatory network analysis of survival-related genes of patients with colorectal cancer

Cited by 10 publications

References 13 publications

STX2 promotes colorectal cancer metastasis through a positive feedback loop that activates the NF-κB pathway

STX2 promotes colorectal cancer metastasis through a positive feedback loop that activates the NF-κB pathway

Specific microRNA–mRNA Regulatory Network of Colon Cancer Invasion Mediated by Tissue Kallikrein–Related Peptidase 6

Genome-wide conditional association study reveals the influences of lifestyle cofactors on genetic regulation of body surface area in MESA population

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