HNF4α, SP1 and c-myc are master regulators of CNS autoimmunity

Colombo, Emanuela; Dario, Marco Di; Menon, Ramesh; Valente, Maria Giovanna; Bassani, Claudia; Sarno, Nicole; Mazza, Davide; Montini, Federico; Moiola, Lucia; Comı, Gıancarlo; Martinelli, Vittorio; Farina, Cinthia

doi:10.1016/j.jaut.2023.103053

Cited by 6 publications

(7 citation statements)

References 45 publications

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“…To comprehensively observe how the enriched ontologies interact with each other, we also built an interaction network of the ontologies, aiming to provide insights into the interplay and potential crosstalk among various biological pathways and cellular components implicated in the condition under investigation. The functional analysis indicated immune processes as the predominant pathways associated with SPMS, consistent with the existing literature and supported by the original authors of the investigated datasets [ 16 , 17 , 18 , 19 , 20 , 21 ]. These DEGs primarily localized on cell surfaces, emphasizing the involvement of immune receptors in MS pathology.…”

Section: Resultssupporting

confidence: 87%

“…Overall, the results we obtained, especially in first steps of our analyses, are supportive of the important role of immune/inflammatory processes in MS, which constituted the main findings of the original works related to the datasets used [ 16 , 17 , 18 , 19 , 20 , 21 ], as many of the top genes found to be up-regulated (please refer to Figure 1 and the Supplementary Materials ) were related to such processes. The datasets’ original studies also greatly described the shared molecular pathways at work in MS pathogenesis, regardless of the subtype, and were informative of the regulatory architecture behind MS-associated altered gene expression.…”

Section: Discussionsupporting

confidence: 80%

“…For our study, we used a subset of subjects from six different databases containing information on gene expression from both brain (GSE126802 [ 16 ] and GSE131282 [ 17 ]) and blood (GSE17048 [ 18 ], E-MTAB-11415 [ 19 ], E-MTAB-4890 [ 20 ], and E-MTAB-5151 [ 21 ]) tissues. We opted to use both brain and blood tissues for our analysis.…”

Section: Discussionmentioning

confidence: 99%

“…The finalized datasets enlisted for the analyses performed on the brain were GSE126802 [ 16 ] and GSE131282 [ 17 ]. The datasets selected for the blood analyses were GSE17048 [ 18 ], E-MTAB-11415 [ 19 ], E-MTAB-4890 [ 20 ], and E-MTAB-5151 [ 21 ]. The above-reported datasets included a total of 116 SPMS samples (41 from brains and 75 from blood) and 175 HCs (23 from brains and 152 from blood).…”

Section: Methodsmentioning

confidence: 99%

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In Silico Analysis Highlights Potential Predictive Indicators Associated with Secondary Progressive Multiple Sclerosis

Calabrò,

Lui,

Mazzon

et al. 2024

IJMS

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Multiple sclerosis (MS) is a complex inflammatory disease affecting the central nervous system. Most commonly, it begins with recurrent symptoms followed by partial or complete recovery, known as relapsing–remitting MS (RRMS). Over time, many RRMS patients progress to secondary progressive MS (SPMS), marked by gradual symptom deterioration. The factors triggering this transition remain unknown, lacking predictive biomarkers. This study aims to identify blood biomarkers specific to SPMS. We analyzed six datasets of SPMS and RRMS patients’ blood and brain tissues, and compared the differential expressed genes (DEGs) obtained to highlight DEGs reflecting alterations occurring in both brain and blood tissues and the potential biological processes involved. We observed a total of 38 DEGs up-regulated in both blood and brain tissues, and their interaction network was evaluated through network analysis. Among the aforementioned DEGs, 21 may be directly involved with SPMS transition. Further, we highlighted three biological processes, including the calcineurin–NFAT pathway, related to this transition. The investigated DEGs may serve as a promising means to monitor the transition from RRMS to SPMS, which is still elusive. Given that they can also be sourced from blood samples, this approach could offer a relatively rapid and convenient method for monitoring MS and facilitating expedited assessments.

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Section: Resultssupporting

confidence: 87%

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

In Silico Analysis Highlights Potential Predictive Indicators Associated with Secondary Progressive Multiple Sclerosis

Calabrò,

Lui,

Mazzon

et al. 2024

IJMS

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“…Finally, bioinformatic analyses of protein-protein interaction networks in MS found common genes and biological pathways for disease susceptibility, among which MYC was found to be a central gene in peripheral blood mononuclear cells from MS patients ( Safari-Alighiarloo et al, 2020 ). A similar study confirmed the role of MYC, along with HNF4α and SP1, as a master regulator of CNS autoimmunity ( Colombo et al, 2023 ). In this case, MYC was inhibited using OTX015, an inhibitor of BET domain proteins that indirectly decreases MYC levels.…”

Section: Myc’s Involvement In Diseases and Conditionssupporting

confidence: 68%

MYC: there is more to it than cancer

Zacarías-Fluck,

Soucek,

Whitfield

2024

Front. Cell Dev. Biol.

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MYC is a pleiotropic transcription factor involved in multiple cellular processes. While its mechanism of action and targets are not completely elucidated, it has a fundamental role in cellular proliferation, differentiation, metabolism, ribogenesis, and bone and vascular development. Over 4 decades of research and some 10,000 publications linking it to tumorigenesis (by searching PubMed for “MYC oncogene”) have led to MYC becoming a most-wanted target for the treatment of cancer, where many of MYC’s physiological functions become co-opted for tumour initiation and maintenance. In this context, an abundance of reviews describes strategies for potentially targeting MYC in the oncology field. However, its multiple roles in different aspects of cellular biology suggest that it may also play a role in many additional diseases, and other publications are indeed linking MYC to pathologies beyond cancer. Here, we review these physiological functions and the current literature linking MYC to non-oncological diseases. The intense efforts towards developing MYC inhibitors as a cancer therapy will potentially have huge implications for the treatment of other diseases. In addition, with a complementary approach, we discuss some diseases and conditions where MYC appears to play a protective role and hence its increased expression or activation could be therapeutic.

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HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer

Zhao,

Tang,

et al. 2024

Evol Bioinform Online

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Background: Intestinal metaplasia (IM) of gastric epithelium has traditionally been regarded as an irreversible stage in the process of the Correa cascade. Exploring the potential molecular mechanism of IM is significant for effective gastric cancer prevention. Methods: The GSE78523 dataset, obtained from the Gene Expression Omnibus (GEO) database, was analyzed using RStudio software to identify the differently expressed genes (DEGs) between IM tissues and normal gastric epithelial tissues. Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Gene Set Enrichment Analysis (GESA), and protein-protein interaction (PPI) analysis were used to find potential genes. Additionally, the screened genes were analyzed for clinical, immunological, and genetic correlation aspects using single gene clinical correlation analysis (UALCAN), Tumor–Immune System Interactions Database (TISIDB), and validated through western blot experiments. Results: Enrichment analysis showed that the lipid metabolic pathway was significantly associated with IM tissues and the apolipoprotein B ( APOB) gene was identified in the subsequent analysis. Experiment results and correlation analysis showed that the expression of APOB was higher in IM tissues than in normal tissues. This elevated expression of APOB was also found to be associated with the expression levels of hepatocyte nuclear factor 4A ( HNF4A) gene. HNF4A was also found to be associated with immune cell infiltration to gastric cancer and was linked to the prognosis of gastric cancer patients. Moreover, HNF4A was also highly expressed in both IM tissues and gastric cancer cells. Conclusion: Our findings indicate that HNF4A regulates the microenvironment of lipid metabolism in IM tissues by targeting APOB. Higher expression of HNF4A tends to lead to a worse prognosis in gastric cancer patients implying it may serve as a predictive indicator for the progression from IM to gastric cancer.

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HNF4α, SP1 and c-myc are master regulators of CNS autoimmunity

Cited by 6 publications

References 45 publications

In Silico Analysis Highlights Potential Predictive Indicators Associated with Secondary Progressive Multiple Sclerosis

In Silico Analysis Highlights Potential Predictive Indicators Associated with Secondary Progressive Multiple Sclerosis

MYC: there is more to it than cancer

HNF4A-Bridging the Gap Between Intestinal Metaplasia and Gastric Cancer

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