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The Potential of Nuclear Pore Complexes in Cancer Therapy.

Nuclear pore complexes (NPCs) play a critical role in regulating transport-dependent gene expression, influencing various stages of cancer development and progression. Dysregulation of nucleocytoplasmic transport has profound implications, particularly in the context of cancer-associated protein mislocalization. This review provides specific information about the relationship between nuclear pore complexes, key regulatory proteins, and their impact on cancer biology. Highlighting the influence of tumor-suppressor proteins as well as the potential of gold nanoparticles and intelligent nanosyste

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… Post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation, and sumoylation, can affect nuclear localization or export signals, preventing proper recognition by transport receptors. …

Leptin, Adiponectin, and Sam68 in Bone Metastasis from Breast Cancer.

The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially those derived from the breast, prostate, and lung. Despite advances in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival and are often responsible for the fatal outcome of the disease. Bone and the bone marrow environment contain a wide variety of cells. No longer

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… Sam68 is regulated at the post-translational level by phosphorylation [ 99 ], acetylation [ 100 ], methylation [ 101 ], and SUMO (small ubiquitin-like modifier) modification (SUMOylation, a post-translational modification analogous to ubiquitylation and involving the addition of SUMOs to proteins instead …

LncRNA Gas5, a Target of the Nonsense-Mediated Decay Pathway in the Brain, Regulates Neuroinflammation and Neurodegenerative Disease Pathways in a Tauopathy Mouse Model.

Dysregulation of target genes of nonsense-mediated decay (NMD) in the brain remains sparsely known in tauopathies. PS19 transgenic mice expressing human mutant P301S tau were evaluated for levels of lncRNA Gas5, a target of NMD. The results show Gas5 decreased in the brains of PS19 mice as they aged. We evaluated the consequences of blocking the NMD-mediated turnover of Gas5 using a small molecule administered intranasally to PS19 mice. The results show NPC86 disassociated Upf1 and Gas5, thereby hindering NMD. NPC86 treatment increased Gas5 levels in the cortex of male PS19 mice concurrent wit

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… treated with NPC86 compared to PBS-treated PS19 mice are (1) signal regulatory protein family interactions (6 DEGs), (2) the glutamate neurotransmitter release cycle (21 DEGs), (3) protein–protein interactions at synapses (63 DEGs), (4) receptor-type tyrosine protein phosphatases (19 DEGs), and (5) sumoylation …

Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.

Osteoblasts are mainly derived from mesenchymal stem cells in the bone marrow. These stem cells can differentiate into osteoblasts, which have the functions of secreting bone matrix, promoting bone formation, and participating in bone remodeling. The abnormality of osteoblasts can cause a variety of bone-related diseases, including osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, with the side effects caused by the application of PTH drugs, biphosphonate drugs, and calmodulin drugs, people have carried out more in-depth research on the mechanism of osteoblast

Exploring the mechanism of rosmarinic acid in the treatment of lung adenocarcinoma based on bioinformatics methods and experimental validation.

ObjectiveRosmarinic acid (RosA) is a natural polyphenol compound that has been shown to be effective in the treatment of inflammatory disease and a variety of malignant tumors. However, its specific mechanism for the treatment of lung adenocarcinoma (LUAD) has not been fully elucidated. Therefore, this study aims to clarify the mechanism of RosA in the treatment of LUAD by integrating bioinformatics, network pharmacology and in vivo experiments, and to explore the potential of the active ingredients of traditional Chinese medicine in treating LUAD.MethodsFirstly, the network pharmacology was u

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… PPARγ sumoylation-mediated lipid accumulation in lung cancer. Oncotarget. 2017;47:82491–505. 10.18632/oncotarget.19700. 88. Hua TNM, Kim MK, Vo VTA, Choi JW, Choi JH, Kim HW, et al. …

miRNA-seq identification and clinical validation of CD138+ and circulating miR-25 in treatment response of multiple myeloma.

BackgroundDespite significant advancements in multiple myeloma (MM) therapy, the highly heterogenous treatment response hinders reliable prognosis and tailored therapeutics. Herein, we have studied the clinical utility of miRNAs in ameliorating patients' management.MethodsmiRNA-seq was performed in bone marrow CD138+ plasma cells (PCs) of 24 MM and smoldering MM (sMM) patients to analyze miRNAs profile. CD138+ and circulating miR-25 levels were quantified using in house RT-qPCR assays in our screening MM/sMM cohort (CD138+ plasma cells n = 167; subcohort of MM peripheral plasma samples n = 69)

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… Du L Liu W Aldana-Masangkay G Pozhitkov A Pichiorri F Chen Y SUMOylation inhibition enhances dexamethasone sensitivity in multiple myeloma J Exp Clin Cancer Res 2022 41 1 8 10.1186/s13046-021-02226-9 34983615 PMC8725350 50. …

Молекулярная основа для человеческой митохондриальной модификации tRNA m3C с помощью альтернативной разбрызгивания METTL8.

METTL8 недавно был определен как катализатор метилпереносазы 3-methylcytidine Биогенез на месте 32 (м3С32) митохондриальных tRNA. METTL8 также потенциально участвует в мRNA метилации и R-loop Biogenesis. Как METTL8 играет многообразную роль в разных камерах, и митохондриальное образование митохондриала tRNA m3C остается неясным. Здесь мы обнаружили, что альтернативное скрещивание mRNA вызвало несколько изоформ METTL8. One (изоформ)METTL8-Iso1) был направлен на митохондрию через N-терминальную предпоследнюю последовательность, в то время как другой one (В тыс.METTL8-Iso4) в основном локализован

Towards Precision Oncology: The Role of Smoothened and Its Variants in Cancer.

The G protein-coupled receptor Smoothened (Smo) is a central signal transducer of the Hedgehog (Hh) pathway which has been linked to diverse forms of tumours. Stimulated by advancements in structural and functional characterisation, the Smo receptor has been recognised as an important therapeutic target in Hh-driven cancers, and several Smo inhibitors have now been approved for cancer therapy. This receptor is also known to be an oncoprotein itself and its gain-of-function variants have been associated with skin, brain, and liver cancers. According to the COSMIC database, oncogenic mutations o

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… Post-translational modifications are now known to regulate Smo activity, with phosphorylation, N-glycosylation, ubiquitination, and recently discovered cholesterylation having particular regulatory importance, although sumoylation has also been described [ 49 ]. …

Proteasome 26S subunit, non-ATPases 1 (PSMD1) and 3 (PSMD3), play an oncogenic role in chronic myeloid leukemia by stabilizing nuclear factor-kappa B.

Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 have revolutionized therapy for chronic myeloid leukemia (CML), paving the way for clinical development in other diseases. Despite success, targeting leukemic stem cells and overcoming drug resistance remain challenges for curative cancer therapy. To identify drivers of kinase-independent TKI resistance in CML, we performed genome-wide expression analyses on TKI-resistant versus sensitive CML cell lines, revealing a nuclear factor-kappa B (NF-κB) expression signature. Nucleocytoplasmic fractionation and luciferase reporter assays confirmed i

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… It was previously reported that PSMD1 functions in the proteasome by acting as an ubiquitin receptor, binding of peptide substrates, and gate opening, which could be subject to several different PTMs (e.g., SUMOylation, N-acetylation, succinylation, and S-glutathionylation) [ 70 ]. …

The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.

Glucocorticoids exert pleiotropic effects on all tissues to regulate cellular and metabolic homeostasis. Synthetic forms are used therapeutically in a wide range of conditions for their anti-inflammatory benefits, at the cost of dose and duration-dependent side effects. Significant variability occurs between tissues, disease states, and individuals with regard to both the beneficial and deleterious effects. The glucocorticoid receptor (GR) is the site of action for these hormones and a vast body of work has been conducted understanding its function. Traditionally, it was thought that the anti-

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… SUMOylation is the addition of small ubiquitin-related modifier-1 (SUMO-1) protein to lysine residues that, while related to ubiquitin, do not immediately signal GR for proteasomal degradation. … SUMOylation has been demonstrated to increase or decrease transcriptional activity of GR depending on the promoter, modification residue, or tissue ( 149 ). …

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted t

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… including small ubiquitin‐like modifier (SUMO), neural precursor cell expressed developmentally downregulated protein 8 (NEDD8), ATG8, ATG12, URM1, UFM1, FAT10, and ISG15. 108 Among them, SUMO and NEDD8 are closely related to p53 modification. 109 The SUMO is a small ubiquitin‐like molecule. 110 The sumoylation … of p53 is mainly mediated by specific SUMO‐E3‐ligase such as TOP1 binding arginine/serine‐rich protein (Topor) and protein inhibitor of activated stat. 111 , 112 Compared with ubiquitination, sumoylation of p53 does not promote the degradation of p53 but inhibits the transcriptional activation of p53 …

Одиссей моноколональных гаммопатий: сосредоточен на прекурсорах и переходе от MGUS и SMM к нескольким Myeloma, с кратким обзором новых терапевтических стратегий.

Моноклональные гаммопатии охватывают континуум от моноклональной гаммопатии неопределенного значения (MMUS) и заморозки нескольких миелом (SMM) до открытой множественной миеломы (MM). Эта постепенная клональная эволюция обусловлена первичными цитогенетическими повреждениями, вторичными геномными явлениями и эпигенетической реконструкцией в допустимой микроокружающей среде костного мозга. Традиционные биомаркеры (коэффициенты сыворотки М-протеина и свободных световых цепей) обеспечивают полезную, но неполную прогнозную информацию, поскольку они не отражают пространственной неоднородности или вр

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… The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome. Blood. 2010;115(14):2827–34. 108. Győrffy B. Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors. …

Mechanistic and Clinical Perspectives on Traditional Chinese Medicine in Thyroid Cancer Management.

Thyroid cancer is one of the most prevalent malignancies of the endocrine system, comprising various subtypes such as papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC), and the aggressive anaplastic thyroid carcinoma (ATC). Despite a generally favorable prognosis for PTC, recurrence, metastasis, and resistance to conventional therapies continue to pose significant challenges. The pathogenesis of thyroid cancer involves genetic mutations in BRAF, RAS, and RET, as well as dysregulated molecular pathways such as MAPK, PI3K/Akt/mTOR, and NF-κB

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… These changes can be either activating or suppressive to gene expression by either activating or repressing gene expression through methylation, acetylation, phosphorylation, ubiquitylation, and sumoylation ( Feng and Meng, 2022 ). …

T-Type Calcium Channels: A Mixed Blessing.

The role of T-type calcium channels is well established in excitable cells, where they preside over action potential generation, automaticity, and firing. They also contribute to intracellular calcium signaling, cell cycle progression, and cell fate; and, in this sense, they emerge as key regulators also in non-excitable cells. In particular, their expression may be considered a prognostic factor in cancer. Almost all cancer cells express T-type calcium channels to the point that it has been considered a pharmacological target; but, as the drugs used to reduce their expression are not complete

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… Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond. J. Mol. Cell. Cardiol. 2014;71:32–42. doi: 10.1016/j.yjmcc.2013.10.008. 101. Pagan J., Seto T., Pagano M., Cittadini A. Role of the ubiquitin proteasome system in the heart. Circ. …

Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.

Genetic and epigenetic changes in DNA are involved in cancer development and tumor progression. Histone deacetylases (HDACs) are key regulators of gene expression that act as transcriptional repressors by removing acetyl groups from histones. HDACs are dysregulated in many cancers, making them a therapeutic target for the treatment of cancer. Histone deacetylase inhibitors (HDACi), a novel class of small-molecular therapeutics, are now approved by the Food and Drug Administration as anticancer agents. While they have shown great promise, resistance to HDACi is often observed and furthermore, H

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… The N-terminal tail of histones can be modified posttranslationally by acetylation, methylation, ubiquitination, phosphorylation, sumoylation, ADP ribosylation, deamination, and proline isomerization ( 1 – 3 ). …

The Ubiquitin-Proteasome System (UPS) as a Cancer Drug Target: Emerging Mechanisms and Therapeutics

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… Regulation of cardiac proteasomes by ubiquitination, SUMOylation, and beyond. J Mol Cell Cardiol. 2014;71:32–42. doi: 10.1016/j.yjmcc.2013.10.008. Cummins JM, Vogelstein B. HAUSP is required for p53 destabilization. Cell Cycle. 2004;3:689–692. …

Natural products targeting ferroptosis in cancer: molecular mechanisms and applications.

Ferroptosis is a novel class of programmed cell death that is mainly dependent on intracellular iron accumulation and lipid peroxidation. Ferroptosis is closely related to a variety of human diseases, especially different kinds of cancer. Several small molecule inducers have been developed to induce ferroptosis in tumor cells, some of which have been used in clinical studies. However, these chemical small molecules have toxic effects that limit its wide application. Natural products, however, have a natural advantage in cancer therapy due to their low toxicity and side effects. Some natural pr

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… Tanshinone IIA destabilizes SLC7A11 by regulating PIAS4-mediated SUMOylation of SLC7A11 through KDM1A, and promotes ferroptosis in breast cancer . J Adv Res . ( 2024 ) 69 : 313–27 . doi: 10.1016/j.jare.2024.04.009 , PMID: 38615741 PMC11954794 24 Liu Y Wan Y Jiang Y Zhang L Cheng W . …

Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

The treatment landscape for multiple myeloma (MM) is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy wi

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… The lysine residues within the N-terminal of histone tails can undergo various chemical modifications, including acetylation, methylation, ubiquitination, phosphorylation, and sumoylation. 54 The acetylation status of histones is controlled by the opposing actions of two classes of enzymes: histone acetyl …

Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.

Cancer therapy and cancer drug discovery and development have been historically focused on specific cancers (tissue/organ of origin). However, with advances in molecular biology and multi-omics of cancer, there is a trend to develop pan-cancer therapeutic modalities. In targeted therapy, pan-cancer strategies target common molecular alterations across different cancer types and specific cancer strategies are tailored to the unique biological characteristics of individual tumor types. Each approach offers distinct advantages and limitations, and understanding these differences is critical in th

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… Finally, other PTMs such as acetylation, palmitoylation, nitrosylation, and sumoylation remain under investigation as additional regulatory checkpoints ( Ahearn et al., 2018 ; Campbell and Philips, 2021 ). … Apart from phosphorylation, PCNA undergoes ubiquitination and SUMOylation, modifications that influence its role in DNA repair and damage tolerance mechanisms ( Maga and Hubscher, 2003 ). Further, PCNA binds numerous proteins, which enhances its functional capabilities. …

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Ne

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… PIAS mainly regulates transcription by blocking STAT DNA-binding activity, promoting transcript factor sumoylation, and recruiting transcriptional co-repressors such as histone deacetylase ( 35 ). PTPs can dephosphorylate STAT and therefore inhibit JAK/STAT signal transduction. …