MYC: there is more to it than cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Март 6, 2024

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

Язык: Английский

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Beyond small molecules: advancing MYC-targeted cancer therapies through protein engineering

Transcription, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Янв. 29, 2025

Protein engineering has emerged as a powerful approach toward the development of novel therapeutics targeting MYC/MAX/E-box network, an active driver >70% cancers. The MYC/MAX heterodimer regulates numerous genes in our cells by binding Enhancer box (E-box) DNA site and activating transcription downstream genes. Traditional small molecules that inhibit MYC face significant limitations include toxic effects, drug delivery challenges, resistance. Recent advances protein offer promising alternatives creating protein-based drugs directly disrupt dimerization interface and/or MYC/MAX's to specific targets. Designed proteins like Omomyc, DuoMyc, ME47, MEF, Mad activity through dimerization, sequestration, DNA-binding mechanisms. Compared molecules, these engineered can superior specificity efficacy provide potential pathway for overcoming traditional cancer therapies. success highlights importance developing treatments.

Язык: Английский

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M1-type microglia-derived exosomes contribute to blood–brain barrier damage

Brain Research, Год журнала: 2024, Номер 1835, С. 148919 - 148919

Опубликована: Апрель 6, 2024

Язык: Английский

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Multitarget mechanism of MYC inhibition by the bacterial lon protease in disease

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 25, 2025

Abstract Identifying specific inhibitors of the MYC oncogene has been challenging, due to off target effects associated with inhibition. This study investigated how recombinant Escherichia coli Lon protease (rLon), which targets in human cells, inhibits over-activation models infection and cancer. In silico predictions identified peptide domains bacterial that affinity these peptides for was by surface plasmon resonance. The N-terminal domain rLon shown interact C-terminal, leucine zipper MAX prevent MYC/MAX dimerization. Furthermore, targeted degraded c-MYC vitro cellular models, through peptidase domain. a model kidney infection, treatment prevented, c-MYC, N-MYC L-MYC over-expression, MYC-dependent gene expression, specifically renal toxicity genes pathology, suggesting recognizes corrects dysregulation this disease. findings describe multitarget mechanism inhibition rLon, combined achieved domains, targeting different epitopes functions, no evidence or detrimental on homeostatic expression.

Язык: Английский

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Exploring common genomic biomarkers to disclose common drugs for the treatment of colorectal cancer and hepatocellular carcinoma with type-2 diabetes through transcriptomics analysis

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0319028 - e0319028

Опубликована: Март 24, 2025

Type 2 diabetes (T2D) is a crucial risk factor for both colorectal cancer (CRC) and hepatocellular carcinoma (HCC). However, so far, there was no study that has investigated common drugs against HCC CRC during their co-occurrence with T2D patients. Consequently, patients often require multiple disease-specific drugs, which can lead toxicities adverse effects to the due drug-drug interactions. This aimed identify genomic biomarkers (cGBs) associated pathogenetic mechanisms underlying CRC, HCC, uncover potential therapeutic compounds these three diseases. Firstly, we identified 86 differentially expressed genes (cDEGs) capable of separating each from control groups based on transcriptomic profiling. Of cDEGs, 37 were upregulated 49 downregulated. Genetic association studies average Log2 fold-change (aLog2FC) cDEGs suggested genetic among T2D. Subsequently, six top-ranked (MYC, MMP9, THBS1, IL6, CXCL1, SPP1) as through protein-protein interaction (PPI) network analysis. Further analysis cGBs GO-terms KEGG pathways revealed shared diseases, including specific biological processes, molecular functions, cellular components signaling pathways. The gene co-regulatory two transcription factors (FOXC1 GATA2) miRNAs (hsa-mir-195-5p, hsa-mir-124a-3p, hsa-mir-34a-5p) transcriptional post-transcriptional regulators cGBs. Finally, cGBs-guided seven candidate (Digitoxin, Camptosar, AMG-900, Imatinib, Irinotecan, Midostaurin, Linsitinib) treatment T2D, docking, cross-validation, ADME/T (Absorption–Distribution–Metabolism–Excretion–Toxicity) Most findings received support by literature review diseases individual studies. Thus, this offers valuable insights researchers clinicians improve diagnosis and/or

Язык: Английский

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Manipulating Myc for reparative regeneration

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Март 21, 2024

The Myc family of proto-oncogenes is a key node for the signal transduction external pro-proliferative signals to cellular processes required development, tissue homoeostasis maintenance, and regeneration across evolution. tight regulation synthesis activity essential restricting its oncogenic potential. In this review, we highlight central role that plays in animal kingdom (from Cnidaria echinoderms Chordata) how could be employed unlock regenerative potential non-regenerative tissues humans therapeutic purposes. Mastering fine balance harnessing ability promote transcription without triggering oncogenesis may open door many exciting opportunities development wide array diseases.

Язык: Английский

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Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells

Cell Reports, Год журнала: 2024, Номер 43(9), С. 114710 - 114710

Опубликована: Сен. 1, 2024

Язык: Английский

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Prognostic Model Identification of Ribosome Biogenesis-Related Genes in Pancreatic Cancer Based on Multiple Machine Learning Analyses

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Background Pancreatic cancer is one of the most aggressive and lethal malignancies within digestive system, characterized by an extremely low five-year survival rate formidable treatment challenges. Ribosome biogenesis a core process in protein synthesis, essential for cell growth, proliferation, survival. Tumors typically exhibit abnormally high proliferation rates, with ribosome often being excessively activated cells to synthesize significant quantity proteins required tumor development. In pancreatic cancer, enhanced may be associated drug resistance malignant phenotypes, presenting it as potential therapeutic target. Therefore, exploring molecular mechanisms uncover new biomarkers targets, facilitating development personalized strategies. Methods biogenesis-related gene signatures were obtained from TCGA database Gene Cards. Multiple machine learning methods employed screen prognostic sets closely related survival, followed construction risk model. The GEO was utilized external validation GSE155698 single-cell RNA sequencing dataset analyzed evaluate expression profiles module scores. Results A total 60 genes identified. Through univariate Cox regression various techniques, nine key (ECT2, CKB, HMGA2, TPX2, ERBB3, SLC2A1, KRT13, PRSS3, CRABP2) selected highly sensitive specific diagnosis prognosis PAAD patients. These demonstrated sensitivity specificity score feature constructed based on found independent factor mortality, advanced clinical pathological features, chemotherapy resistance. Additionally, this progression-related pathways, suggesting its role promoting through ribosomal division, mitosis-related processes, microtubule cytoskeleton organization. Furthermore, immunosuppressive infiltration immune checkpoint expression, indicating microenvironment. Single-cell revealed higher CRABP2, PRSS3 ductal epithelial cells. Conclusions This study provides insights into connections between characteristics microenvironment, responses. research underscores critical progression offering valuable perspectives evaluation response prediction cancer.

Язык: Английский

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Overexpression of lncRNA TINCR inhibits cutaneous squamous cell carcinoma cells through promotes methylation of Myc and TERC genes

Archives of Dermatological Research, Год журнала: 2025, Номер 317(1)

Опубликована: Март 12, 2025

Long non-coding RNA (lncRNA) TINCR has been shown to play a crucial regulatory role in various tumors. However, its specific mechanism of action cutaneous squamous cell carcinoma (CSCC) remains unclear. This study aimed explore the lncRNA CSCC. We utilized overexpression techniques effects on CSCC cells. Methylation-specific PCR (MSP) and immunoprecipitation (RIP) assays were used assess impact methylation promoter regions Myc TERC genes, interaction with DNA methyltransferase 1 (DNMT1). The results showed that significantly promoted (N-MYC, L-MYC, c-MYC) inhibiting proliferation, migration, invasion MSP RIP experiments further confirmed binds DNMT1, enhancing levels genes. These findings suggest may serve as potential therapeutic target for by regulating key oncogenes. provide new insights into molecular mechanisms highlight targeting TINCR.

Язык: Английский

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MYC: Master Regulator of Cell Death and Tumor Progression

IntechOpen eBooks, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

MYC gene has become one of the most investigated oncogenes for regulating programmed cell death and tumor growth. is a transcription factor that regulates expression numerous genes involved in critical cellular processes, such as metabolism, stress response, proliferation. However, its dysfunction, often caused by amplifications or translocations, makes it potent oncogenic driver, contributing to uncontrolled growth, angiogenesis, invasiveness, metastasis. Paradoxically, can promote both survival elimination through activation apoptotic mechanisms, creating delicate balance between death. This chapter explores dual role regulator life death, analyzing molecular mechanisms determine activity different biological contexts. The main pathways controlled MYC, contribution plasticity, interactions with other suppressors will be discussed. Finally, emerging therapeutic strategies aimed at targeting regulatory networks reviewed, along challenges translating this knowledge into clinical interventions. A thorough understanding biology crucial develop innovative therapies improve treatment aggressive resistant tumors.

Язык: Английский

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