Translational Advances in Oncogene and Tumor-Suppressor Gene Research

Cancers, Journal Year: 2025, Volume and Issue: 17(6), P. 1008 - 1008

Published: March 17, 2025

Cancer, characterized by the uncontrolled proliferation of cells, is one leading causes death globally, with approximately in five people developing disease their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology progression, there still a significant gap knowledge about genetic aberrations nuclear DNA damage. The study two critical groups genes—tumor suppressors, which inhibit promote apoptosis, oncogenes, regulate survival—can help to understand genomic behind tumorigenesis, more personalized approaches diagnosis treatment. Aberration tumor undergo two-hit loss-of-function mutations, activated forms proto-oncogenes that experience one-hit gain-of-function are responsible for dysregulation key signaling pathways cell division, such as p53, Rb, Ras/Raf/ERK/MAPK, PI3K/AKT, Wnt/β-catenin. Modern breakthroughs genomics research, like next-generation sequencing, have provided efficient strategies mapping unique changes contribute heterogeneity. Novel therapeutic enabled medicine, helping address variability suppressors oncogenes. This comprehensive review examines molecular mechanisms tumor-suppressor they regulate, epigenetic modifications, heterogeneity, drug resistance drive carcinogenesis. Moreover, explores clinical application sequencing techniques, multiomics, diagnostic procedures, pharmacogenomics, treatment prevention options, discussing future directions emerging technologies.

Language: Английский

---

Tamoxifen induces protection against manganese toxicity by REST upregulation via the ER-α/Wnt/β-catenin pathway in neuronal cells

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108529 - 108529

Published: April 1, 2025

Chronic exposure to elevated levels of manganese (Mn) causes a neurological disorder referred as manganism, with symptoms resembling Parkinson's disease (PD). The repressor element-1 silencing transcription factor (REST) has been shown be neuroprotective in several disorders, including PD, suggesting that identifying REST upregulation mechanisms is an important avenue for the development novel therapeutics. 17β-estradiol (E2) activates Wnt/β-catenin signaling, which known increase transcription. E2 and tamoxifen (TX), selective estrogen receptor modulator, exerted protection against Mn toxicity. In this study, we tested if TX upregulates potentially via signaling Cath.a-differentiated (CAD) neuronal cells using luciferase assay, qPCR, western blot analysis, immunocytochemistry, mutagenesis, chromatin immunoprecipitation, electrophoretic mobility shift assay. (1 μM) increased promoter activities mRNA/protein attenuated Mn-decreased parallel TX's protective effects (250 μM)-induced toxicity, Wnt. activated by preventing β-catenin degradation inactivation glycogen synthase kinase-3 beta, leading its nuclear translocation binding T-cell factor/lymphoid enhancer sites on Wnt- responsive elements (WRE) promoter. Mutation WRE abolished TX-induced activity. Wnt activation was primarily (ER)-α, although ER-β G protein-coupled 1 also mediated action These findings underscore critical role transcription, affording toxicity disorders associated dysfunction.

Language: Английский

---

A comprehensive review of PRAME and BAP1 in melanoma: Genomic instability and immunotherapy targets

Cellular Signalling, Journal Year: 2024, Volume and Issue: unknown, P. 111434 - 111434

Published: Sept. 1, 2024

Language: Английский

---

The importance of the circRNA/Wnt axis in gliomas: biological functions and clinical opportunities

Pathology - Research and Practice, Journal Year: 2024, Volume and Issue: 261, P. 155510 - 155510

Published: July 31, 2024

Language: Английский

---

Pharmacological Enhancement of Adult Hippocampal Neurogenesis Improves Behavioral Pattern Separation in Young and Aged Mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 4, 2024

Abstract BACKGROUND Impairments in behavioral pattern separation (BPS)—the ability to distinguish between similar contexts or experiences—contribute memory interference and overgeneralization seen many neuropsychiatric conditions, including depression, anxiety, PTSD, dementia, age-related cognitive decline. While BPS relies on the dentate gyrus is sensitive changes adult hippocampal neurogenesis (AHN), its significance as a pharmacological target has not been tested. METHODS In this study, we applied human neural stem cell high-throughput screening cascade identify compounds that increase neurogenesis. One compound with favorable profile, RO6871135, was then tested mice. RESULTS Chronic treatment 7.5 mg/kg increased AHN improved fear discrimination task both young aged RO6871135 also lowered innate anxiety-like behavior, which more apparent mice exposed chronic corticosterone. Ablation of by irradiation supported neurogenesis-dependent mechanism for RO6871135-induced improvements BPS. To possible mechanisms action, vitro vivo kinase inhibition chemical proteomics assays were performed. These tests indicated inhibited CDK8, CDK11, CaMK2a, CaMK2b, MAP2K6, GSK3b. An analog demonstrated high affinity CONCLUSIONS studies demonstrate method empirical identification preclinical testing novel neurogenic can improve BPS, points be interrogated development new therapies specific endophenotypes such impaired

Language: Английский

---

Potential of olfactory neuroepithelial cells as a model to study schizophrenia: A focus on GPCRs (Review)

International Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 53(1)

Published: Nov. 28, 2023

Schizophrenia (SZ) is a multifactorial disorder characterized by volume reduction in gray and white matter, oxidative stress, neuroinflammation, altered neurotransmission, as well molecular deficiencies such punctual mutation Disrupted‑in‑Schizophrenia 1 protein. In this regard, it essential to understand the underlying disturbances determine pathophysiological mechanisms of disease. The signaling pathways activated G protein‑coupled receptors (GPCRs) are key SZ. Convenient models need be designed validated study these processes at cellular level. Cultured olfactory stem cells used investigate neural alterations related pathophysiology Multipotent human undifferentiated express GPCRs involved numerous physiological functions proliferation, differentiation bioenergetics. use obtained from patients with SZ may identify GPCR that underlie dysfunctional both specialized neurons or derived neuroglia. present review aimed analyze role their Culture epithelial constitutes suitable model other psychiatric disorders

Language: Английский

---

Cellular and Molecular Mechanisms Underlying Synaptic Subcellular Specificity

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(2), P. 155 - 155

Published: Feb. 2, 2024

Chemical synapses are essential for neuronal information storage and relay. The synaptic signal received or sent from spatially distinct subcellular compartments often generates different outcomes due to the distance physical property difference. Therefore, final output of postsynaptic neurons is determined not only by type intensity inputs but also location. How specificity has long been focus study in neurodevelopment field. Genetic studies invertebrates such as Caenorhabditis elegans (C. elegans) have uncovered important molecular cellular mechanisms required specificity. Interestingly, similar were found mammalian cerebellum, hippocampus, cerebral cortex. This review summarizes comprehensive advances underlying specificity, focusing on C. rodents.

Language: Английский

---

Investigating How Inflammation Involving NF-κB Signaling Disrupts the Genetic Architecture of Neurons/Neural Stem Cells and Fuels Neurodegeneration

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 26, 2024

Abstract Background: Understanding how inflammation disrupts neural stem cells and neuronal genetic architecture is crucial. This investigation explores these mechanisms, aiming to decipher the role of in disrupting architecture. Unraveling complexities may reveal therapeutic targets, offering hope for precision interventions impede or slow progression debilitating neurodegenerative conditions. Methods: Databases including PubMed, MEDLINE Google Scholar were searched published articles without any date restrictions, involving NF-κB neurogenic genes/signaling pathways/transcription factors. They investigated study unravel (NSCs) architecture, this process fuels development neurodegeneration. adheres relevant PRISMA guidelines (Preferred Reporting Items Systematic Reviews Meta-Analyses). Results: reveals activation plays a central inflammation-induced disruption, mediating transcriptional dysregulation key factors like Ngn1, NeuroD, PDGF, compromising code. Downregulation neurotrophic factors, notably BDNF, increases vulnerability apoptotic pathways, accelerating Inflammatory processes extend genomic landscape, affecting genes crucial neurogenesis synaptic function, contributing observed dysfunction diseases. Furthermore, NSCs, impairing progenitor dynamics, diminishing regenerative potential nervous system. Identified strategies include targeting NF-κB, restoration support, promoting proper gene expression neurogenesis, promising avenues mitigating damage halting progression. Conclusion: investigates intricate impact on providing insights into pathogenesis NF-κB-mediated disruptions compromise impair induce dysfunction, enhance apoptosis. orchestrated contributes Therapeutically, promotion emerge as mitigate damage, cascade.

Language: Английский

---

Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study

Journal of Neurology, Journal Year: 2024, Volume and Issue: 271(11), P. 7250 - 7263

Published: Sept. 12, 2024

Language: Английский

---

Modulation of the central nervous system immune response and neuroinflammation via Wnt signaling in health and neurodegenerative diseases

Ibrain, Journal Year: 2024, Volume and Issue: 10(4), P. 462 - 476

Published: Dec. 1, 2024

Abstract The immune response in the central nervous system (CNS) is a highly specialized and tightly regulated process essential for maintaining neural health protecting against pathogens injuries. primary cells within CNS include microglia, astrocytes, T cells, B cells. They work together, continuously monitor environment signs of infection, injury, or disease, respond by phagocytosing debris, releasing cytokines, recruiting other In addition to providing neuroprotection, these responses must be carefully balanced prevent excessive inflammation that can lead neuronal damage contribute neurodegenerative diseases. Dysregulated are implicated various diseases such as Alzheimer's Parkinson's amyotrophic lateral sclerosis. Wnt signaling crucial pathway regulates cellular processes critical brain development, function, maintenance. Despite enhancing CNS, dysregulated exacerbates neuroinflammation brains. This review summarized role regulating under different conditions. We then examined healthy brains during development also discussed therapeutic intervention through modulation highlighted challenges limitations current clinical trials.

Language: Английский

---