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

Cancer Cell International, Journal Year: 2024, Volume and Issue: 24(1)

Published: March 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

Language: Английский

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Insights into the Molecular Mechanisms Mediating Extravasation in Brain Metastasis of Breast Cancer, Melanoma, and Lung Cancer

Cancers, Journal Year: 2023, Volume and Issue: 15(8), P. 2258 - 2258

Published: April 12, 2023

Brain metastasis is an incurable end-stage of systemic cancer associated with poor prognosis, and its incidence increasing. occurs through a multi-step cascade where cells spread from the primary tumor site to brain. The extravasation blood–brain barrier (BBB) critical step in brain metastasis. During extravasation, circulating roll along endothelium (BE), adhere it, then induce alterations endothelial transmigrate BBB enter Rolling adhesion are generally mediated by selectins molecules induced inflammatory mediators, while proteolytic enzymes, including matrix metalloproteinase, transmigration factors, chemokines. However, molecular mechanisms mediating not yet fully understood. A better understanding these essential as it may serve basis for development therapeutic strategies prevention or treatment metastases. In this review, we summarize events that occur during three types most likely develop metastasis: breast cancer, melanoma, lung cancer. Common driving different tumors discussed.

Language: Английский

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A comprehensive outline of the role of non-coding RNAs in vitiligo

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 41, P. 101916 - 101916

Published: Jan. 9, 2025

Language: Английский

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Assessment of miR-19b-3p, miR-182-5p, and miR-155-5p expression and its relation

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: March 22, 2025

Language: Английский

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miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1737 - 1737

Published: Feb. 1, 2024

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment many cancers, although high number patients fail to respond ICIs, which is partially due ability tumor cells evade system surveillance. Non-coding microRNAs (miRNAs) have been shown modulate evasion cells, and there thus growing interest elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis response ICIs. We therefore performed an extensive literature analysis evaluate clinical utility with confirmed direct relationship As result this systematic review, we stratified miRNA landscape into (i) whose levels directly (ii) expression modulated by (iii) that elicit toxic effects participate immune-related adverse events (irAEs) caused

Language: Английский

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Molecular Markers in Melanoma Progression: A Study on the Expression of miRNA Gene Subtypes in Tumoral vs. Benign Nevi

Current Oncology, Journal Year: 2024, Volume and Issue: 31(5), P. 2881 - 2894

Published: May 17, 2024

This study investigates the differential expression of miRNA gene subtypes in tumoral versus benign nevi individuals with melanoma, aiming to identify clinically significant correlations that could serve as reliable markers for assessing tumor stage and progression. Conducted between 2019 2022, this descriptive, quantitative observational research analyzed 90 formalin-fixed paraffin-embedded (FFPE) samples from Pius Brinzeu County Emergency Clinical Hospital, Timisoara, including 45 advanced-stage melanoma pigmented nevi. purification analysis were performed using miRNeasy Kit Human Cancer PathwayFinder miScript PCR Array, statistical (including logistic regression) determine associations cancer staging, such high Breslow index risk, number mitoses, vascular invasion. After comparison 180 subtypes, we selected 10 most upregulated downregulated genes. The results revealed hsa-miR-133b, hsa-miR-335-5p, hsa-miR-200a-3p, hsa-miR-885-5p significantly samples, fold changes ranging 1.09 1.12. Conversely, hsa-miR-451a hsa-miR-29b-3p showed notable downregulation 0.90 0.92, respectively. Additionally, regression identified (OR = 2.51) hsa-miR-200a-3p 2.10) associated an increased risk a index, while hsa-miR-127-3p reduced risk. Conclusively, underscores alterations compared highlights potential specific miRNAs biomarkers identification characteristics suggests their utility developing non-invasive, cost-effective diagnostic tools guiding therapeutic decisions, potentially improving patient outcomes management.

Language: Английский

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Decoding the Promise and Challenges of miRNA-Based Cancer Therapies: An Essential Update on miR-21, miR-34, and miR-155

International Journal of Medical Sciences, Journal Year: 2024, Volume and Issue: 21(14), P. 2781 - 2798

Published: Oct. 28, 2024

MicroRNAs (miRNAs)-based therapies hold great promise for cancer treatment, challenges such as expression variability, off-target effects, and limited clinical effectiveness have led to the withdrawal of many trials. This review investigates setbacks in miRNA-based by examining miR-21, miR-34, miR-155, highlighting their functional complexity, delivering these effectively. Moreover, It highlights recent advances delivery methods, combination therapies, personalized treatment approaches overcome challenges. intricate molecular networks involving miRNAs, particularly interactions with other non-coding RNAs, long RNAs (lncRNAs) circular (circRNAs), emphasizing pivotal role miRNAs biology therapeutic strategies. By addressing hurdles, this aims steer future research toward harnessing potential miRNA target pathways effectively, enhance anti-tumor responses, ultimately improve patient outcomes precision therapy.

Language: Английский

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Paradigm of biomarkers in metastatic melanoma (Review)

Oncology Letters, Journal Year: 2024, Volume and Issue: 29(2)

Published: Nov. 26, 2024

Metastatic melanoma is an aggressive and deadly form of skin cancer, known for its rapid ability to spread other organs. Melanoma metastasis involves several steps: Local invasion, lymphovascular invasion proliferation new sites. This process facilitated by genetic alterations, interactions with the tumor microenvironment evasion immune system. Despite advances in therapies, 5‑year survival rate remains low at ~22.5%. Notably, current research focused on identifying patients who may benefit from specific treatments, considering factors such as mutational load programmed death ligand 1 expression. BRAF inhibitors checkpoint have improved survival, although numerous do not respond or develop resistance, underscoring need novel biomarkers optimize treatment monitoring disease. In summary, purpose present article review different serological, histological, microRNA circulating cell that proven useful diagnosis, follow‑up prognosis metastatic melanoma. These represent a promising area clinical application, aim offering more precise personalized treatments.

Language: Английский

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Multiple Genetic Polymorphisms within microRNA Targets and Homologous microRNA-Binding Sites: Two More Factors Influencing microRNA-Mediated Regulation of Gene Expression

IntechOpen eBooks, Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 14, 2023

miRNA-mRNA interaction depends on multiple factors such as 3’UTR isoforms, the cell and tissue-specific expression levels of RNA-binding proteins, sequence context around mRNA target site, other mechanisms. Genetic polymorphisms within miRNAs their sites appear to be among most important ones because they influence mode outcome universally irreversibly. SNP disruption binding sites, well conformational changes preventing access miRNA its are adopted credible mechanistic explanations SNP-mediated effects. The occurrence SNPs same miRNA-binding site implies combinatorial action. presence repetitive (homologous) for may both enhance targeting provide backup instead one disrupted by SNP, thus rescuing functionality. While being underexplored, genetic homologous considered additional influencing miRNA-mediated regulation gene expression.

Language: Английский

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The HCV-Melanoma Paradox: First Multi-Cohort and Molecular Net-Work Analysis Reveals Lower Incidence but Worse Outcomes—Integrating Clinical, Real-World, and in Silico Data

Medicina, Journal Year: 2024, Volume and Issue: 60(9), P. 1531 - 1531

Published: Sept. 19, 2024

Background and Objectives: The relationship between hepatitis C virus (HCV) infection melanoma remains poorly understood. This study aimed to investigate the association HCV melanoma, assess outcomes in patients with both conditions, explore potential molecular mechanisms connecting two diseases. Materials Methods: We conducted a retrospective cohort of 142 patients, including 29 HCV-related cirrhosis, analyzed their clinical outcomes. For external validation, we used TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched per group. An silico analysis was performed identify pathways linking melanoma. Results: In cohort, HCV-positive showed an increased risk early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% 39.8%, 0.020), mortality 23.0%, < 0.001) compared HCV-negative patients. data revealed that had 53% lower developing (RR 0.470, 95% CI: 0.443–0.498, 0.001). However, higher all-cause (HR 1.360, 1.189–1.556, identified key players, IL-6 CTLA4, HCV-melanoma network. Conclusions: While may be associated development, who develop have poorer provide targets for future research therapeutic interventions.

Language: Английский

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