MicroRNAs as regulators of immune checkpoints in cancer immunotherapy: targeting PD-1/PD-L1 and CTLA-4 pathways

Cancer Cell International, Год журнала: 2024, Номер 24(1)

Опубликована: Март 10, 2024

Abstract Immunotherapy has revolutionized cancer treatment by harnessing the power of immune system to eliminate tumors. Immune checkpoint inhibitors (ICIs) block negative regulatory signals that prevent T cells from attacking cells. Two key ICIs target PD-1/PD-L1 pathway, which includes programmed death-ligand 1 (PD-L1) and its receptor death (PD-1). Another ICI targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). While have demonstrated remarkable efficacy in various malignancies, only a subset patients respond favorably. MicroRNAs (miRNAs), small non-coding RNAs regulate gene expression, play crucial role modulating checkpoints, including CTLA-4. This review summarizes latest advancements immunotherapy, highlighting therapeutic potential targeting CTLA-4 checkpoints miRNAs these pathways. Consequently, understanding complex interplay between is essential for developing more effective personalized immunotherapy strategies treatment. Graphical

Язык: Английский

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The role of microRNAs in the gastric cancer tumor microenvironment

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 20, 2024

Gastric cancer (GC) is one of the deadliest malignant tumors with unknown pathogenesis. Due to its treatment resistance, high recurrence rate, and lack reliable early detection techniques, a majority patients have poor prognosis. Therefore, identifying new tumor biomarkers therapeutic targets essential. This review aims provide fresh insights into enhancing prognosis GC by summarizing processes through which microRNAs (miRNAs) regulate microenvironment (TME) highlighting their critical role in TME. A comprehensive literature was conducted focusing on interactions among cells, extracellular matrix, blood vessels, cancer-associated fibroblasts, immune cells within The noncoding RNAs, known as miRNAs, modulating TME various signaling pathways, cytokines, growth factors, exosomes specifically examined. Tumor formation, metastasis, therapy are significantly influenced miRNAs progression these multiple exosomes. Dysregulation affects cellular such cell proliferation, differentiation, angiogenesis, contributing pathogenesis GC. play crucial regulation TME, influencing patient By understanding mechanisms control potential can be identified improve

Язык: Английский

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Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review

Medicine, Год журнала: 2025, Номер 104(5), С. e41379 - e41379

Опубликована: Янв. 31, 2025

Tumor-associated macrophages (TAMs) are present in and important components of the tumor microenvironment (TME). TAMs differentiate into 2 functionally distinct morphologies, classically activated (M1)-type alternatively (M2)-type TAMs, when stimulated by different cytokines. The types exhibit properties functions. M1 secrete high levels pro-inflammatory chemotactic factors, exerting proinflammatory, antitumor effects. Conversely, M2 alter extracellular matrix, facilitate cellular immune escape, stimulate angiogenesis, thereby promoting anti-inflammatory responses growth. ratio to TME is closely related prognosis tumor. Tumor cells other can regulate polarization thus promote progression through secretion various substances; however, polarized also act on exosomes, forming a positive feedback loop. Therefore, modulating phenotype or blocking might be new approach for cancer treatment. However, intracellular signaling pathways involved poorly understood. AKT pathway an polarization, growth, proliferation, recruitment, apoptosis as well action within TME. This paper reviews regulation provides ideas immunotherapy.

Язык: Английский

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Chronic Gastrointestinal Disorders and miRNA-Associated Disease: An Up-to-Date

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 413 - 413

Опубликована: Янв. 6, 2025

Chronic gastrointestinal disorders such as inflammatory bowel diseases (IBDs) and irritable syndrome (IBS) impose significant health burdens globally. IBDs, encompassing Crohn’s disease ulcerative colitis, are multifactorial characterized by chronic inflammation of the tract. On other hand, IBS is one principal tract functional abdominal pain altered habits. Although precise etiopathogenesis these remains unclear, mounting evidence suggests that non-coding RNA molecules play crucial roles in regulating gene expression associated with inflammation, apoptosis, oxidative stress, tissue permeability, thus influencing progression. miRNAs have emerged possible reliable biomarkers, they can be analyzed biological fluids patients at a low cost. This review explores IBDs IBS, focusing on their involvement control hallmarks. By an extensive literature employing bioinformatics tools, we identified frequently studied concerning diseases. Ultimately, specific could proposed diagnostic biomarkers for IBS. Their ability to secreted into biofluids makes them promising candidates non-invasive tools. Therefore, understanding molecular mechanisms through ways which regulate immune responses provide new insights pathogenesis open avenues miRNA-based therapeutic interventions.

Язык: Английский

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A novel insight into cancer therapy: Lipid metabolism in tumor-associated macrophages

International Immunopharmacology, Год журнала: 2024, Номер 135, С. 112319 - 112319

Опубликована: Май 26, 2024

The tumor immune microenvironment (TIME) can limit the effectiveness and often leads to significant side effects of conventional cancer therapies. Consequently, there is a growing interest in identifying novel targets enhance efficacy targeted therapy. More research indicates that tumor-associated macrophages (TAMs), originating from peripheral blood monocytes generated bone marrow myeloid progenitor cells, play crucial role (TME) are closely associated with resistance traditional Lipid metabolism alterations have been widely recognized as having impact on tumors their microenvironment. Lipids, lipid derivatives, key substances metabolic pathways influence carcinogenesis progression cells by modulating phenotype, function, activity TAMs. Therefore, this review focuses reprogramming microenvironment, which TAMs especially concentrated. Such changes activation polarization, thereby affecting cell response treatment. Furthermore, article explores potential targeting supplementary approach It reviews evaluates current strategies for enhancing through TAMs' proposes new synergistic options chemo-radiotherapy immunotherapy. These efforts aim stimulate further area.

Язык: Английский

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The role of m6A modification during macrophage metabolic reprogramming in human diseases and animal models

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 18, 2025

Macrophage metabolic reprogramming refers to the process by which macrophages adjust their physiological pathways meet survival and functional demands in different immune microenvironments. This involves a range of pathways, including glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, fatty oxidation, cholesterol transport. By modulating expression activity key enzymes molecules within these can make transition between pro- anti-inflammatory phenotypes, thereby linking inflammatory responses progression several diseases, such as atherosclerosis, bowel disease (IBD), acute lung injury (ALI). N6-methyladenosine (m6A) modification has emerged critical regulatory mechanism during macrophage reprogramming, broadly affecting RNA stability, translation, degradation. Therapeutic strategies targeting m6A regulate onset diseases influencing changes, for instance, small molecule inhibitors methyltransferase-like 3 (METTL3) affect glucose metabolism inhibit IBD. review systematically explores recent findings on role molecular mechanisms human animal models, underscoring its potential therapeutic target diseases.

Язык: Английский

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Transcription factor ONECUT3 regulates HDAC6/HIF-1α activity to promote the Warburg effect and tumor growth in colorectal cancer

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Март 3, 2025

The Warburg effect, also known as aerobic glycolysis, plays a crucial role in the onset and progression of colorectal cancer (CRC), although its mechanism remains unclear. In this study, bioinformatics analysis public databases combined with validation using clinical specimens identified transcription factor ONECUT3 key regulator related to effect CRC. Functionally, silencing reverses suppresses tumor growth. Importantly, promotes growth glycolysis-dependent manner through hypoxia-inducible 1α (HIF-1α). Mechanistically, does not directly regulate expression HIF-1α but instead inhibits acetylation via histone deacetylase 6 (HDAC6). This deacetylation enhances transcriptional activity HIF-1α, ultimately upregulating multiple glycolysis-related genes downstream thereby driving facilitating These findings reveal novel by which regulates CRC suggest that targeting may offer promising therapeutic strategy for

Язык: Английский

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Analysis of mutually exclusive expression in cancer cells identifies a previously unknown intergenic regulatory paradigm

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

Mutual exclusion of gene expression has received limited attention. Gene (expression) plasticity analysis provides an efficient way to identify highly plastic genes (HPGs) based on changes in rank. In this study, we quantitatively measured the 19 961 protein‐coding 24 human cancer cell lines and identified HPGs these cells. By comparing methods, showed that virtual sorting cosine similarity, rather than Pearson Spearman rank correlations, are suitable for mutual exclusion. Mutually exclusive pairs were each type. Experimental validation thiol methyltransferase 1B ( TMT1B ; also known as METTL7B ) CD274 molecule PD‐L1 mutually exclusively expressed at either mRNA or protein level. negatively regulated several types, JAK/STAT3 pathway was involved. Knockdown Huh7 cells inhibited interleukin 2 (IL‐2) secretion by Jurkat co‐culture experiments, inhibition blocked anti‐PD‐L1 antibodies. Therefore, study method expressional implies a newly intergenic regulatory paradigm.

Язык: Английский

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Monocitos, macrófagos y células dendríticas en homeostasis y patología

Medicine - Programa de Formación Médica Continuada Acreditado, Год журнала: 2025, Номер 14(28), С. 1629 - 1642

Опубликована: Март 1, 2025

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MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11

Cancers, Год журнала: 2023, Номер 15(17), С. 4342 - 4342

Опубликована: Авг. 30, 2023

Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development progression. The tumor suppressor ability miR-148a-3p has been reported for several cancers. Nevertheless, the role in CRC remains largely undetermined. Here, we aim at investigating molecular mechanisms regulatory targets death mechanism(s). To this end, was evaluated SW480 SW620 cells normal colon epithelial CCD 841 CoN quantitative real-time polymerase chain reaction (qRT-PCR). Data a reduction compared to non-tumor (p < 0.05). Overexpression miR-148a selectively inhibited viability 0.001), while weakly affecting survival At cellular level, mimics promoted apoptotic via caspase-3 activation accumulation mitochondrial reactive oxygen species (ROS) membrane depolarization 0.001). Moreover, overexpression induced lipid peroxidation 0.01), GPX4 downregulation ferroptosis as revealed by intracellular iron ACSL4/TFRC/Ferritin modulation. In addition, levels SLC7A11 mRNA protein, predicted bioinformatic tools, were suppressed miR-148a-3p's overexpression. On contrary, boosted gene ferroptosis. Together, these vitro findings reveal that can function targeting activating ferroptosis, opening new perspectives rationale therapeutic strategies through miR-148a-3p/SLC7A11 pathway.

Язык: Английский

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