Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 19, 2023

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism transmembrane transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, other specific molecules activate JAK-STAT signaling drive a series physiological pathological processes, including proliferation, metabolism, immune response, inflammation, malignancy. Dysregulated related genetic mutations are strongly associated activation cancer progression. Insights into structures functions have led development approval diverse drugs for clinical treatment diseases. Currently, been developed mainly target commonly divided three subtypes: cytokine or receptor antibodies, JAK inhibitors, STAT inhibitors. And novel agents also continue be tested in preclinical studies. effectiveness safety each kind drug warrant further scientific trials before put being applications. Here, we review current understanding fundamental composition function pathway. We discuss advancements JAK-STAT–related pathogenic mechanisms; targeted therapies various diseases, especially disorders, cancers; newly inhibitors; challenges directions field.

Язык: Английский

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Genus Paeonia monoterpene glycosides: A systematic review on their pharmacological activities and molecular mechanisms

Phytomedicine, Год журнала: 2024, Номер 127, С. 155483 - 155483

Опубликована: Фев. 28, 2024

Язык: Английский

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Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers

Breast Cancer Research, Год журнала: 2023, Номер 25(1)

Опубликована: Март 7, 2023

Abstract Background Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the receptor (PRLR) can activate transcription factor STAT5, thus, we examined association between plasma and risk by tumor expression of PRLR, upstream kinase JAK2. Methods Using data from 745 cases 2454 matched controls in Nurses’ Health Study, conducted polytomous logistic regression examine (> 11 ng/mL vs. ≤ ng/mL) measured within 10 years diagnosis PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), JAK2 (pJAK2; C) expression. Analyses were separately premenopausal ( n = 168 cases, 765 controls) postmenopausal women 577 1689 controls). Results In women, levels > positively tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02–5.22) pSTAT5-C 1.64, 1.01–2.65), but not that negative these markers 0.98, 0.65–1.46 OR 0.73, 0.43–1.25; p-heterogeneity 0.06 0.02, respectively). This was stronger when both 2.88, 1.14–7.25). No observed or pJAK2 (positive negative) among women. Among irrespective pSTAT5, (all ≥ 0.21). Conclusion We did observe clear differences pJAK2, although associations pSTAT5 only. While additional studies are needed, this suggests may act on human development through alternative pathways.

Язык: Английский

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A new class of anti-proliferative activity and apoptotic inducer with molecular docking studies for a novel of 1,3-dithiolo[4,5-b]quinoxaline derivatives hybrid with a sulfonamide moiety

RSC Advances, Год журнала: 2023, Номер 13(18), С. 12589 - 12608

Опубликована: Янв. 1, 2023

A new series of 6-(pyrrolidin-1-ylsulfonyl)-[1,3]dithiolo[4,5-

Язык: Английский

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PRMT6 methylation of STAT3 regulates tumor metastasis in breast cancer

Cell Death and Disease, Год журнала: 2023, Номер 14(10)

Опубликована: Окт. 9, 2023

Overcoming distant metastasis stands as a paramount challenge in enhancing the outcomes of breast cancer treatments. Thus, delving deeper into comprehending intricate mechanisms underlying becomes imperative, offering potential avenues for pioneering therapeutic approaches. PRMT6, an arginine N-methyltransferase, possesses ability to methylate both histone and non-histone proteins. It has been reported that methylation proteins impacts their cellular localization, stability, activation, consequently influencing tumor progression. However, extent which PRMT6-mediated protein influences cell metastasis, particularly context cancer, remains elusive. In this study, we established PRMT6 exerted positive regulatory influence on through vivo vitro experiments. Mechanistically, innovatively revealed asymmetrically di-methylated STAT3 at 729 (STAT3 R729me2a). This modification proved indispensable STAT3's membrane its interaction with JAK2, Y705 phosphorylation, PRMT6-driven metastasis. From clinical perspective, unearthed promising R729me2a robust prognostic marker predicting overall survival time patients. terms intervention, demonstrated significant capability inhibitor, EPZ020411, curtail vitro. sum, our study unveils pivotal biological role underscores prospective utility inhibitors effective strategies against STAT3-driven metastatic cancer.

Язык: Английский

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Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer

Molecular and Cellular Biochemistry, Год журнала: 2024, Номер 480(1), С. 1 - 17

Опубликована: Март 22, 2024

Язык: Английский

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STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases

International Reviews of Immunology, Год журнала: 2024, Номер 43(6), С. 394 - 418

Опубликована: Авг. 26, 2024

Signal transducer and activator of transcription (STAT) 4 STAT6 play a crucial role in immune cells by transducing signals from specific cytokine receptors, inducing genes involved cell-mediated humoral immunity. These two different defense mechanisms against pathogens are regulated CD4+ T helper (Th) known as Th1 Th2 cells. Many studies have shown that several diseases including cancer, inflammatory, autoimmune allergic associated with Th1/Th2 imbalance caused increased or decreased expression/activity STAT4 often due to genetic epigenetic aberrances. An altered expression has been observed tumors diseases, while dysregulation signaling pathway is frequently conditions, such atopic dermatitis, asthma, food allergy, Hodgkin non-Hodgkin lymphomas. Recently, dysregulations SARS-CoV2 monkeypox infections, which still public health emergencies many countries. SARS-CoV-2 can induce an responses predominant activation the cytosol nuclei pneumocytes drives polarization storm. In infection virus promote evasion response turn inhibits essential for elimination. Furthermore, variations risk developing systemic lupus erythematosus seem infection.

Язык: Английский

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Single-Cell RNA Sequencing Reveals Extensive Heterogeneity and Unique Gene Trajectories in Non-Transformed and Transformed Human Lung Epithelial Cells: Insights into the Role of LncRNAs in Tumor Heterogeneity

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1690 - 1690

Опубликована: Фев. 16, 2025

Lung cancer exhibits substantial inter- and intra-tumor heterogeneity, with features that present significant challenges in advancing biomarker discovery the development of targeted therapeutics. To fill this gap, we employed single-cell RNA sequencing (scRNA-seq) advanced bioinformatics tools to evaluate transcriptomic heterogeneity immortalized, non-transformed (BEAS2B) transformed (H460) lung epithelial cell lines their responses carcinogen challenge. Gene expression profiles resolved four primary clusters further discretized into unique subclusters based on genetic signatures phenotypic profiles. Profiles long non-coding RNAs (lncRNAs) identified microRNA host genes, antisense divergent transcript, intergenic as contributors cellular heterogeneity. These findings indicate distinct patterns gene expression, remarkably lncRNAs, define versus cells. can be exploited for therapies directed at specific subpopulations precancerous lesions within tumors.

Язык: Английский

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Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer

iScience, Год журнала: 2023, Номер 26(11), С. 108218 - 108218

Опубликована: Окт. 17, 2023

Triple-negative breast cancer (TNBC) poses a considerable challenge due to its aggressive nature. Notably, metal ion-induced cell death, such as ferroptosis, has garnered significant attention and demonstrated potential implications for cancer. Recently, cuproptosis, potent death pathway reliant on copper, been identified. However, whether cuproptosis can be targeted treatment remains uncertain. Here, we screened the US Food Drug Administration (FDA)-approved drug library identified zinc pyrithione (ZnPT) compound that significantly inhibited TNBC progression. RNA sequencing revealed ZnPT disrupted copper homeostasis. Furthermore, facilitated oligomerization of dihydrolipoamide S-acetyltransferase, landmark molecule cuproptosis. Clinically, high expression levels cuproptosis-related proteins were correlated with poor prognosis in patients. Collectively, these findings indicate induce by targeting disrupting homeostasis, providing experimental foundation exploring target discovery

Язык: Английский

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Pharmacological impact of microRNAs in head and neck squamous cell carcinoma: Prevailing insights on molecular pathways, diagnosis, and nanomedicine treatment

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Май 3, 2023

Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of epithelial cells lips, larynx, nasopharynx, mouth, or oro-pharynx. It one deadly forms cancer. About to two percent all neo-plasm-related deaths are attributed head carcinoma, which responsible for about six cancers. MicroRNAs play critical role in proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, other physiological process. regulate gene expression provide new diagnostic, prognostic, therapeutic options carcinoma. In this work, molecular signaling pathways related emphasized. We also an overview MicroRNA downregulation overexpression its as diagnostic prognostic marker recent years, nano-based therapies have been explored. addition, nanotechnology-based alternatives discussed promising strategy exploring paradigms aimed at improving efficacy conventional cytotoxic chemotherapeutic agents against attenuating their cytotoxicity. This article provides information on ongoing recently completed clinical trials based nanotechnology.

Язык: Английский

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