The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers

Jahangiri, Leila; Pucci, Perla; Ishola, Tala; Trigg, Ricky M; Williams, John A.; Pereira, João D.; Cavanagh, Megan L; Turner, Suzanne D.; Gkoutos, Georgios V.; Tsaprouni, Loukia

doi:10.3390/ijms22168527

Cited by 16 publications

(10 citation statements)

References 83 publications

(148 reference statements)

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“…This list was also validated against the GSEA database under the gene sets/ hallmarks module, and revealed the enrichment of 'hallmark MYC target genes' (p-value: 2.47 × 10 −5 , q-value: 1.24 × 10 −3 ) including HSPE1, RUVBL2 and SSBP1 [23,24]. This result was interesting, since links between MYC-regulated proteins, lncRNAs and miRNAs have been extensively reported in the literature [40]. Given these results, the gene networks formed by these 12 selected ECM-related genes with other genes, lncRNAs and miRNAs were investigated.…”

Section: Ssbp1mentioning

confidence: 74%

Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics

Jahangiri

2022

Onco

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A complex interaction occurs between cancer cells and the extracellular matrix (ECM) in the tumour microenvironment (TME). In this study, the expressions and mutational profiles of 964 ECM-related genes and their correlations with patient overall survival (OS) in neuroblastoma, an aggressive paediatric malignancy, were investigated using cBioPortal and PCAT databases. Furthermore, extended networks comprising protein-protein, protein-long non-coding RNA (lncRNA), and protein-miRNA of 12 selected ECM-related genes were established. The higher expressions of 12 ECM-related genes, AMBN, COLQ, ELFN1, HAS3, HSPE1, LMAN1, LRP5, MUC6, RAMP2, RUVBL2, SSBP1 and UMOD in neuroblastoma patients displayed a significant correlation with patient OS, while similar associations with neuroblastoma patient risk groups, histology and MYCN amplification were obtained. Furthermore, extended gene networks formed by these 12 ECM-related genes were established using Cytoscape, STRING, MSigDB/BioGRID, GeneMANIA and Omicsnet. Finally, the implications of the 12 ECM-related genes in other cancers were revealed using GEPIA2 and the Human Pathology Atlas databases. This meta-analysis showed the significance of these 12 ECM-related genes as putative prognostic predictors in neuroblastoma and other cancers.

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Section: Ssbp1mentioning

confidence: 74%

Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics

Jahangiri

2022

Onco

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“…Like MYC , CTNNB1 also had increased expression in AD (logfc of 0.021 and 0.026 in Morabito and Lau, respectively; Fig 5A ). Both CTNNB1 and MYC are involved in the WNT signaling pathway [58], which was decreased in AD ( Fig 5C ). Interestingly, despite their divergent gene expression patterns (downregulated in Morabito, upregulated in Lau; Fig 5A ), TP53 and its transcriptional cofactor EP300 [59] function as transcriptional repressors in AD ( Fig 5B ), which is further recapitulated by decreased p53 signaling pathway activity in inhibitory neurons ( Fig 5C ).…”

Section: Resultsmentioning

confidence: 99%

Altered Glia-Neuron Communication in Alzheimer’s Disease Affects WNT, p53, and NFkB Signaling Determined by snRNA-seq

Soelter,

Howton,

Clark

et al. 2023

Preprint

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BackgroundAlzheimer’s disease is the most common cause of dementia and is characterized by amyloid-β plaques, tau neurofibrillary tangles, and neuronal loss. Although neuronal loss is a primary hallmark of Alzheimer’s disease, it is known that non-neuronal cell populations are ultimately responsible for maintaining brain homeostasis and neuronal health through neuron-glia and glial cell crosstalk. Many signaling pathways have been proposed to be dysregulated in Alzheimer’s disease, including WNT, TGFβ, p53, mTOR, NFkB, and Pi3k/Akt signaling. Here, we predict altered cell-cell communication between glia and neurons.MethodsUsing public snRNA-sequencing data generated from postmortem human prefrontal cortex, we predicted altered cell-cell communication between glia (astrocytes, microglia, oligodendrocytes, and oligodendrocyte progenitor cells) and neurons (excitatory and inhibitory). We confirmed interactions in an independent orthogonal dataset. We determined cell-type-specificity using Jaccard Similarity Index and investigated the downstream effects of altered interactions in inhibitory neurons through gene expression and transcription factor activity analyses of signaling mediators. Finally, we determined changes in pathway activity in inhibitory neurons.ResultsCell-cell communication between glia and neurons is altered in Alzheimer’s disease in a cell-type-specific manner. As expected, ligands are more cell-type-specific than receptors and targets. We validated 51 ligand- receptor pairs in an independent dataset that included two known Alzheimer’s disease risk genes:APPandAPOE. 17 (14 upregulated and 3 downregulated in Alzheimer’s disease) of the 51 interactions also had the same downstream target gene. Most of the signaling mediators of these interactions were not differentially expressed, however, the mediators that are also transcription factors had differential activity between AD and control. Namely,MYCandTP53, which are associated with WNT and p53 signaling, respectively, had repressor activity in Alzheimer’s disease, along with decreased WNT and p53 activity in inhibitory neurons. Additionally, inhibitory neurons had both increased NFkB signaling pathway activity and activator activity ofNFIL3, an NFkB signaling-associated transcription factor.ConclusionsCell-cell communication between glia and neurons in Alzheimer’s disease is altered in a cell-type-specific manner involving Alzheimer’s disease risk genes. Signaling mediators had altered transcription factor activity suggesting altered glia-neuron interactions may dysregulate signaling pathways including WNT, p53, and NFkB in inhibitory neurons.

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“…According to currently available studies, HUWE1 plays a key role in regulating autophagy and other biological functions in many cancers, including DNA damage response, transcription, autophagy, apoptosis, and metabolism [ 20 ]. Transcription factor MYC plays a central role in cancer by inducing autophagy [ 21 ]. EIF4G2 is a kind of eukaryotic translation initiation factor that indirectly participates in the regulation of autophagy in cancer [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Reveals an Association between Autophagy, Prognosis, Tumor Microenvironment, and Immunotherapy in Osteosarcoma

Tong

et al. 2022

Journal of Oncology

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Autophagy is a catabolic pathway involved in the regulation of bone homeostasis. We explore clinical correlation of autophagy-related key molecules to establish risk signature for predicting the prognosis, tumor microenvironment (TME), and immunotherapy response of osteosarcoma. Single cell RNA sequencing data from GSE162454 dataset distinguished malignant cells from normal cells in osteosarcoma. Autophagy-related genes (ARGs) were extracted from the established risk signature of the Molecular Signatures Database of Gene Set Enrichment Analysis (GSEA) by univariate Cox and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Overall survival (OS), TME score, abundance of infiltrating immune cells, and response to immune-checkpoint blockade (ICB) treatment in patients with different risks were compared based on risk score. Nine ARGs were identified and risk signature was constructed. In all osteosarcoma datasets, the OS was significantly longer in the high-risk patients than low-risk onset. Risk signature significantly stratified clinical outcomes, including OS, metastatic status, and survival status. Risk signature was an independent variable for predicting osteosarcoma OS and showed high accuracy. A nomogram based on risk signature and metastases was developed. The calibration curve confirmed the consistency in 1-year, 3-year, and 5-year predicted OS and the actual OS. The risk score was related to 6 kinds of T cells and macrophages, myeloid-derived suppressor cell, natural killer cell, immune score, and stromal score in TME. The risk signature helped in predicting patients’ response to anti-PD1/anti-PD-L1 treatment. The ARGs-led risk signature has important value for survival prediction, risk stratification, tumor microenvironment, and immune response evaluation of osteosarcoma.

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The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers

Cited by 16 publications

References 83 publications

Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics

Profiling of the Prognostic Role of Extracellular Matrix-Related Genes in Neuroblastoma Using Databases and Integrated Bioinformatics

Altered Glia-Neuron Communication in Alzheimer’s Disease Affects WNT, p53, and NFkB Signaling Determined by snRNA-seq

Bioinformatics Analysis Reveals an Association between Autophagy, Prognosis, Tumor Microenvironment, and Immunotherapy in Osteosarcoma

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