Regulatory T cells subgroups in the tumor microenvironment cannot be overlooked: Their involvement in prognosis and treatment strategy in melanoma

Environmental Toxicology, Год журнала: 2024, Номер 39(10), С. 4512 - 4530

Опубликована: Март 26, 2024

Abstract Background Melanoma, the most lethal form of skin cancer, presents substantial challenges despite effective surgical interventions for in situ lesions. Regulatory T cells (Tregs) wield a pivotal immunomodulatory influence within tumor microenvironment, yet their impact on melanoma prognosis and direct molecular interactions with remain elusive. This investigation employs single‐cell analysis to unveil intricate nature Tregs human melanoma. Methods Single‐cell RNA bulk sequencing data, alongside clinical information, were obtained from public repositories. Initially, GO GSEA analyses employed delineate functional disparities among distinct cell subsets. Pseudotime cell–cell interconnection conducted, followed by an endeavor construct prognostic model grounded Treg‐associated risk scores. model's efficacy was demonstrated via PCA K‐M analyses, multivariate Cox regression affirming its independent value patients. Furthermore, immune infiltration analysis, checkpoint gene expression scrutiny, drug sensitivity assessments performed ascertain relevance this model. Results Following batch effect correction, 80 025 partitioned into 31 clusters, encompassing B cells, plasma endothelial fibroblasts, monocytes, macrophages, T_NK cells. Within these, 4240 CD4+ subclassified seven types. Functional underscored function elucidating Treg subpopulations. Notably, ITGB2 signaling pathway emerged as plausible nexus linking Our signature exhibited robust predictive capacities potential implications evaluating immunotherapy response. Conclusion exert critical role suppression revealing molecular‐level association innovative Treg‐centered introduces promising marker melanoma, holding future assessments.

Язык: Английский

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RSL3 induces ferroptosis by activating the NF-κB signalling pathway to enhance the chemosensitivity of triple-negative breast cancer cells to paclitaxel

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

Опубликована: Янв. 11, 2025

Chemotherapy resistance in triple-negative breast cancer (TNBC) leads to poor therapeutic effects and a prognosis. Given that paclitaxel-based chemotherapy is the main treatment method for TNBC, enhancing its chemosensitivity has been research focus. Induced ferroptosis of tumour cells proven increase chemosensitivity, but ability sensitize TNBC paclitaxel (PTX) unknown. In our experiments, measurements viability proliferation validated synergistic effect PTX combined with RSL3 on cells. The accumulation intracellular Fe2+ lipid reactive oxygen species, as well expression malondialdehyde, illustrated enhanced by inducing ferroptosis. Through transcriptome sequencing, series differentially expressed genes were identified, which cytokines, such CXCLs, was significantly increased group, combination therapy enriched mainly NFκB signalling pathway. subsequent validation use NF-κB inhibitor BAY11-7082 reversed inhibitory cell activity. xenograft immunodeficient mouse model, vivo further verified. Our both vitro, activating pathway, thereby increasing PTX. This study provides new insights improving efficacy strategies.

Язык: Английский

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TRP channels and breast cancer: the role of TRPs in the pathophysiological development

Frontiers in Molecular Biosciences, Год журнала: 2025, Номер 12

Опубликована: Фев. 26, 2025

TRP channels play important roles in regulating various physiological and pathological processes, including the progression of cancer. Several mediate tumour development. This review focuses on role development breast cancer, their involvement proliferation, apoptosis, autophagy, metastasis, angiogenesis. are associated with carcinogenesis as potential therapeutic targets prognostic biomarkers is under investigation. summarizes reported effects inhibiting or agonizing channel cancer cells. Although there relatively mature protocols for treatment its not currently a breakthrough, therapies targeting may be developable strategy it.

Язык: Английский

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Gliotoxin Triggers Cell Death Through Multifaceted Targeting of Cancer-Inducing Genes in Breast Cancer Therapy

Computational Biology and Chemistry, Год журнала: 2024, Номер 112, С. 108170 - 108170

Опубликована: Авг. 13, 2024

Язык: Английский

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Inhibition of XIST restrains paclitaxel resistance in breast cancer cells by targeting hsa-let-7d-5p/ATG16L1 through regulation of autophagy

Cellular Signalling, Год журнала: 2024, Номер unknown, С. 111534 - 111534

Опубликована: Дек. 1, 2024

Breast cancer is a fatal malignant tumor in women worldwide. The development of paclitaxel resistance remains challenge. Autophagy considered to have significant part the chemotherapeutic stress mechanism. This study aimed investigate function long non-coding RNA (lncRNA) breast cell chemoresistance and autophagy. (PTX)-resistant cells were established. X-inactive specific transcript (XIST) was demonstrated using vitro vivo experiments. Transmission electron microscope (TEM) used observe autophagy vesicles. Protein mRNA levels determined western blotting quantitative real time polymerase chain reaction (qRT-PCR). We discovered that autophagic activity correlated with PTX-resistant cells. In studies showed XIST inhibition reduced paclitaxel, caused be suppressed by regulating hsa-let-7d-5p ATG16L1 expression. Mechanically, threonine protein kinase B (PKB; also known as AKT) - mammalian target rapamycin (mTOR) pathway activated when knockdown XIST, while reversed hsa-let-7d-5p. Our results verified played role developing via mediating It may potential for treatment strategies.

Язык: Английский

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UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation

Translational Oncology, Год журнала: 2024, Номер 52, С. 102241 - 102241

Опубликована: Дек. 13, 2024

Язык: Английский

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CENPA facilitates glioma stem cell stemness and suppress ferroptosis to accelerate glioblastoma multiforme by promoting GBP2 transcription

Pathology - Research and Practice, Год журнала: 2024, Номер 260, С. 155438 - 155438

Опубликована: Июнь 28, 2024

Язык: Английский

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