Dataset Information

MicroRNA-105 is involved in TNF-?-related tumor microenvironment enhanced colorectal cancer progression.

ABSTRACT: TNF-? is a central proinflammatory cytokine contributing to malignant tumor progression in tumor microenvironment. In this study, we found the upregulation of miR-105 in colorectal cancer was associated with aggressive phenotype, and the enhanced expression of miR-105 was required for TNF-?-induced epithelial-mesenchymal transition (EMT). The expression of miR-105 was remarkably stimulated by TNF-? in a time-dependent manner using real-time qPCR analysis. Inhibition of miR-105 remarkably weakened the aggressive effects of TNF-? through preventing the activation of NF-?B signaling and the initiation of EMT. Furthermore, miR-105 was demonstrated directly targeted on the 3'-UTRs of RAP2C, a Rap2 subfamily of small GTP-binding protein. Consistently, suppression of RAP2C stimulated the role of miR-105, which dramatically promoted the invasion and metastasis of CRC cells. Thalidomide, a TNF-? and NF-?B inhibitor, significantly weakened the metastasis and homing capacity of miR-105-overexpressed CRC cells in nude mice. Our investigation initiatively illustrated the modulatory role of miR-105 in TNF-?-induced EMT and further CRC metastasis. We also offer a better understanding of TNF?-induced metastasis and suggest an effective therapeutic strategy against CRC metastasis.

SUBMITTER: Shen Z

PROVIDER: S-EPMC5870598 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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MicroRNA-105 is involved in TNF-α-related tumor microenvironment enhanced colorectal cancer progression.

Shen Zetao Z Zhou Rui R Liu Chen C Wang Yaofeng Y Zhan Wanqi W Shao Ziyun Z Liu Jian J Zhang Feifei F Xu Lijun L Zhou Xinying X Qi Lu L Bo Feng F Ding Yanqing Y Zhao Liang L

Cell death & disease 20171213 12

TNF-α is a central proinflammatory cytokine contributing to malignant tumor progression in tumor microenvironment. In this study, we found the upregulation of miR-105 in colorectal cancer was associated with aggressive phenotype, and the enhanced expression of miR-105 was required for TNF-α-induced epithelial-mesenchymal transition (EMT). The expression of miR-105 was remarkably stimulated by TNF-α in a time-dependent manner using real-time qPCR analysis. Inhibition of miR-105 remarkably weakene ...[more]

PMID: 29238068

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Project description:BackgroundThe tumor microenvironment (TME) has significantly correlation with tumor occurrence and prognosis. Our study aimed to identify the prognostic immune-related genes (IRGs)in the tumor microenvironment of colorectal cancer (CRC).MethodsTranscriptome and clinical data of CRC cases were downloaded from TCGA and GEO databases. Stromal score, immune score, and tumor purity were calculated by the ESTIMATE algorithm. Based on the scores, we divided CRC patients from the TCGA database into low and high groups, and the differentially expressed genes (DEGs) were identified. Immune-related genes (IRGs) were selected by venn plots. To explore underlying pathways, protein-protein interaction (PPI) networks and functional enrichment analysis were used. After utilizing LASSO Cox regression analysis, we finally established a multi-IRGs signature for predicting the prognosis of CRC patients. A nomogram consists of the thirteen-IRGs signature and clinical parameters was developed to predict the overall survival (OS). We investigated the association between prognostic validated IRGs and immune infiltrates by TIMER database.ResultsGene expression profiles and clinical information of 1635 CRC patients were collected from the TCGA and GEO databases. Higher stromal score, immune score and lower tumor purity were observed positive correlation with tumor stage and poor OS. Based on stromal score, immune score and tumor purity, 1517 DEGs, 1296 DEGs, and 1892 DEGs were identified respectively. The 948 IRGs were screened by venn plots. A thirteen-IRGs signature was constructed for predicting survival of CRC patients. Nomogram with a C-index of 0.769 (95%CI, 0.717-0.821) was developed to predict survival of CRC patients by integrating clinical parameters and thirteen-IRGs signature. The AUC for 1-, 3-, and 5-year OS were 0.789, 0.783 and 0.790, respectively. Results from TIMER database revealed that CD1B, GPX3 and IDO1 were significantly related with immune infiltrates.ConclusionsIn this study, we established a novel thirteen immune-related genes signature that may serve as a validated prognostic predictor for CRC patients, thus will be conducive to individualized treatment decisions.

Dataset Information

MicroRNA-105 is involved in TNF-?-related tumor microenvironment enhanced colorectal cancer progression.

Publications

MicroRNA-105 is involved in TNF-α-related tumor microenvironment enhanced colorectal cancer progression.

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