A Negative Feedback Loop Between NAMPT and TGF-β Signaling Pathway in Colorectal Cancer Cells

Lv, Xiaoqun; Zhang, Jinguo; Zhang, Jun; Guan, Wencai; Ren, Weifang; Liu, Yujuan; Xu, Guoxiong

doi:10.2147/ott.s282367

Cited by 10 publications

(5 citation statements)

References 38 publications

(47 reference statements)

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“…For example, CTSD, which is highly expressed in CRC tissues, is closely associated with a poor prognosis by promoting β-catenin pathway (Ding et al, 2022). Moreover, NAMPT is overexpressed in CRC tissues and is associated with a poor prognosis by stabilizing the protein components of Smad2, Smad3, and Smad4 in the TGF-β signaling pathway, thereby increasing the activity of the TGF-β signaling (Lv et al, 2021). S100A8 promotes CRC metastasis by increasing epithelialmesenchymal transition and promoting the TGF-β signaling pathway Frontiers in Genetics frontiersin.org (Li et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of autophagy-related genes based on single-cell RNA-sequencing in colorectal cancer

et al. 2023

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Background: Colorectal cancer (CRC) is the second most common cancer in China. Autophagy plays an important role in the initiation and development of CRC. Here, we assessed the prognostic value and potential functions of autophagy-related genes (ARGs) using integrated analysis using single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) and RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA).Methods: We analyzed GEO-scRNA-seq data from GEO using various single-cell technologies, including cell clustering, and identification of differentially expressed genes (DEGs) in different cell types. Additionally, we performed gene set variation analysis (GSVA). The differentially expressed ARGs among different cell types and those between CRC and normal tissues were identified using TCGA-RNA-seq data, and the hub ARGs were screened. Finally, a prognostic model based on the hub ARGs was constructed and validated, and patients with CRC in TCGA datasets were divided into high- and low-risk groups based on their risk-score, and immune cells infiltration and drug sensitivity analyses between the two groups were performed.Results: We obtained single-cell expression profiles of 16,270 cells, and clustered them into seven types of cells. GSVA revealed that the DEGs among the seven types of cells were enriched in many signaling pathways associated with cancer development. We screened 55 differentially expressed ARGs, and identified 11 hub ARGs. Our prognostic model revealed that the 11 hub ARGs including CTSB, ITGA6, and S100A8, had a good predictive ability. Moreover, the immune cell infiltrations in CRC tissues were different between the two groups, and the hub ARGs were significantly correlated with the enrichment of immune cell infiltration. The drug sensitivity analysis revealed that the patients in the two risk groups had difference in their response to anti-cancer drugs.Conclusion: We developed a novel prognostic 11-hub ARG risk model, and these hubs may act as potential therapeutic targets for CRC.

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Section: Discussionmentioning

confidence: 99%

Prognostic value of autophagy-related genes based on single-cell RNA-sequencing in colorectal cancer

et al. 2023

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“…VEGFA-VEGFR2 Signaling Pathway [27], TGF-beta Signaling Pathway [24], Negative regulation of NOTCH4 signaling. There is already evidence that morphine promotes tumorigenesis and cetuximab resistance through EGFR signal activation in human colorectal cancer [28].…”

Section: Discussionmentioning

confidence: 99%

“…such as Cell cycle, DNA replication, P53 Signaling pathway [17], and VEGF Signaling pathway [18], were enriched in high NMB phenotypes. KEGG signaling pathways were enriched in low NMB phenotypes, including Colorectal cancer, ERBB Signaling pathway [19], JAK-STAT Signaling pathway [20], MAPK Signaling pathway [21], MTOR Signaling pathway [22], NOTCH Signaling pathway [23], pancreatic cancer, pathways in cancer, TGF-BETA Signaling pathway [24], and WNT Signaling pathway [25].…”

Section: Discussionmentioning

confidence: 99%

NMB as a Novel Prognostic Biomarker in Colorectal Cancer Correlating with Immune Infiltrates

Fan

Liang

Wang

et al. 2022

Preprint

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Background:Neuromedin B(NMB) is associated with the occurrence and development of a variety of cancers, However, the role of NMB in colorectal cancer is lacking in further studies.Methods:Transcriptome data and clinical data of CRC were downloaded and analyzed from the TCGA database and GEO database to study the differential expression of NMB. We analyzed the relationship between NMB expression and survival in patients with colorectal cancer using 8 public datasets from the Gene Expression Integration (GEO) database and the TCGA database. Meta-analysis was performed on the analysis results of TCGA and GEO data to determine the role of NMB in CRC. The receiver operating characteristic (ROC) curve was used to evaluate the accuracy of NMB in predicting survival rate in CRC patients. Wilcox. Test and Kruskal. Tests were used to study the relationship between clinicopathological features and the expression of NMB. Cox regression analysis was used to analyze the effect of NMB expression on survival. Gene collection enrichment analysis (GSEA) was performed using the TCGA database to screen the signaling pathway regulated by NMB. The Linkedomics platform was used to identify NMB co-expressed genes and explore the potential mechanisms of NMB mediation. Tumor Immune Estimation Resource (TIMER) site database was used to analyze the relationship between NMB expression level and immune infiltration. Related genes were identified by co-expression analysis, and four genes (NDUFB10, SERF2, DPP7, and NAPRT) were screened out as a prognostic signature. The relationship between risk score and OS were studied to explore the predictive value of risk score for CRC. Nomogram was constructed to predict 1 - and 3-year survival in colorectal cancer patients.Results:NMB was highly expressed in colorectal cancer, suggested a poor prognosis. The ROC curve proved that NMB had a high accuracy in predicting the survival rate of CRC patients. Multivariate regression analysis demonstrated that NMB was an independent predictor of survival in patients with CRC.GSEA identified the pathways involved in NMB regulation, including the P53 Signaling pathway, VEGF Signaling pathway, JAK-STAT Signaling pathway, MAPK Signaling pathway,mTOR Signaling pathway, TGF-BETA Signaling pathway, and WNT Signaling pathway, etc. Then,6512 co-expressed genes were identified through the Linkedomics Platform to investigate the potential mechanisms of NMB regulation, including Hepatocellular carcinoma cell cycle, EGF/EGFR Signaling Pathway, VEGFA-VEGFR2 Signaling Pathway, etc. We also conclude that NMB is correlated with T cells CD8, T cells CD4 memory resting, Macrophages M0. Different mutational forms of NMB were associated with the immune infiltration of 6 leukocytes. We determined the relationship between NMB and immune marker sets in colorectal cancer, such as CCR7, CD3E, CTLA4, HAVCR2, HLA-DPB1. The predictive ability of the risk score was significantly better than that of T, N, and M stages. A new nomogram for predicting the 1-year and 3-year OS of CRC patients was constructed, showing good reliability and accuracy for improved treatment decisions. In addition, NMB may contribute to drug resistance in CRC.Conclusion:NMB is highly expressed in CRC and provides a potential biomarker for the diagnosis and prognosis of CRC.

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“…The literature review revealed that the vast majority of the identified genes had previously been linked to colorectal cancer pathogenesis. Of these genes, the ones that seem to have an important role in CRC are EZH2, PTEN, EGFR, IGF1, HGF, SMAD4 and PTGS2 [ 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ].…”

Section: In Silico Analysis Of Crc Exosomal Lncrna/circrna–mirna–targ...mentioning

confidence: 99%

Insights on the Biomarker Potential of Exosomal Non-Coding RNAs in Colorectal Cancer: An In Silico Characterization of Related Exosomal lncRNA/circRNA–miRNA–Target Axis

Mezher

Abdallah

Ashekyan

et al. 2023

Cells

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Colorectal cancer (CRC) is one of the most common cancer types, ranking third after lung and breast cancers. As such, it demands special attention for better characterization, which may eventually result in the development of early detection strategies and preventive measures. Currently, components of bodily fluids, which may reflect various disease states, are being increasingly researched for their biomarker potential. One of these components is the circulating extracellular vesicles, namely, exosomes, which are demonstrated to carry various cargo. Of importance, the non-coding RNA cargo of circulating exosomes, especially long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and micro RNAs (miRNAs), may potentially serve as significant diagnostic and prognostic/predictive biomarkers. In this review, we present existing evidence on the diagnostic and prognostic/predictive biomarker value of exosomal non-coding RNAs in CRC. In addition, taking advantage of the miRNA sponging functionality of lncRNAs and circRNAs, we demonstrate an experimentally validated CRC exosomal non-coding RNA-regulated target gene axis benefiting from published miRNA sponging studies in CRC. Hence, we present a set of target genes and pathways downstream of the lncRNA/circRNA–miRNA–target axis along with associated significant Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, which may collectively serve to better characterize CRC and shed light on the significance of exosomal non-coding RNAs in CRC diagnosis and prognosis/prediction.

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A Negative Feedback Loop Between NAMPT and TGF-β Signaling Pathway in Colorectal Cancer Cells

Cited by 10 publications

References 38 publications

Prognostic value of autophagy-related genes based on single-cell RNA-sequencing in colorectal cancer

Prognostic value of autophagy-related genes based on single-cell RNA-sequencing in colorectal cancer

NMB as a Novel Prognostic Biomarker in Colorectal Cancer Correlating with Immune Infiltrates

Insights on the Biomarker Potential of Exosomal Non-Coding RNAs in Colorectal Cancer: An In Silico Characterization of Related Exosomal lncRNA/circRNA–miRNA–Target Axis

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