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Current Role of micrornas in the Diagnosis and Clinical Management of Germ Cell Tumors

Surgical Pathology Clinics 2025年第1期18卷 91-100页

作者： Tavares, Nuno Tiago Henrique, Rui Jerónimo, Carmen Lobo, João Cancer Biology and Epigenetics Group IPO Porto Research Center (GEBC CI-IPOP) Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (P.CCC) & CI-IPOP@RISE (Health Research Network) IPO Porto Research Center CI-LAB3 1st Floor F Building. Rua Dr. António Bernardino de Almeida Porto 4200-072 Portugal Doctoral Programme in Biomedical Sciences ICBAS - School of Medicine and Biomedical Sciences University of Porto Rua Jorge Viterbo Ferreira 228 Porto 4050-513 Portugal Department of Pathology and Molecular Immunology ICBAS - School of Medicine and Biomedical Sciences University of Porto Rua Jorge Viterbo Ferreira 228 Porto 4050-513 Portugal Department of Pathology Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (P.CCC) R. Dr. António Bernardino de Almeida Porto 4200-072 Portugal

AbstractGerm cell tumors (GCTs) are a rare and heterogeneous group of neoplasms arising from primitive germ cells. micrornas are small noncoding RNAs that have emerged as potential cancer biomarkers in the last decade. In particular, miR-371a-3p has shown good diagnostic performance for germ cell neoplasia in situ-derived testicular GCTs in several well-established cohorts and is expected to enter the clinical arena in the near future. GCTs universally exhibit high expression of miR-371-373 and miR-302/367 clusters and low expression of let-7 family miRNAs. Further studies are needed to assess the potential role of these miRNAs as biomarkers of ovarian and extragonadal GCTs.

关键词： Biomarkers Germ cell tumors Liquid biopsies micrornas miR-371a-3p Testicular cancer

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The role of peripheral blood micrornas in the pathogenesis and treatment response of age-related macular degeneration

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FUTURE SCIENCE OA 2025年第1期11卷 2482499页

作者： Kong, Meng Li, Jingwen Tong, Nianting Univ Hlth & Rehabil Sci Qingdao Hosp Qingdao Municipal Hosp Dept Ophthalmol 1 Jiaozhou Rd Qingdao 266011 Shandong Peoples R China Qingdao Univ Sch Med Qingdao Shandong Peoples R China

Age-related macular degeneration is a leading cause of vision loss in aging populations, driven by complex interactions between genetic, environmental, and molecular factors. micrornas have emerged as crucial regulators of cellular processes such as oxidative stress, inflammation, and angiogenesis, all of which contribute to AMD pathogenesis. This narrative review aims to summarize the involvement of peripheral blood micrornas in the pathogenesis of AMD, focusing on key pathways such as oxidative stress, inflammation, and angiogenesis. Additionally, it explores their potential as biomarkers for predicting treatment response, particularly to anti-VEGF therapies. The potential of miRNAs as noninvasive biomarkers for early diagnosis and personalized treatment strategies is also explored, highlighting future directions for research.

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Extracellular vesicles derived micrornas as non-invasive markers of liver fibrosis in chronically infected HCV patients: a pilot study

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NON-CODING RNA RESEARCH 2025年 12卷 132-140页

作者： Cairoli, Victoria Valle-Millares, Daniel Ryan, Pablo Dominguez, Lourdes Martin-Carbonero, Luz de los Santos, Ignacio De Matteo, Elena Ameigeiras, Beatriz De Sousa, Marcela Briz, Veronica Preciado, Maria, V Fernandez-Rodriguez, Amanda Valva, Pamela Ricardo Gutierrez Childrens Hosp Multidisciplinary Inst Invest Pediat Pathol IMIPP Pathol Div Lab Mol BiolCONICETGCB C1425EFD Buenos Aires Argentina Hlth Inst Carlos III ISCIII Natl Ctr Microbiol CNM Unit Viral Infect & Immun Madrid 28222 Spain Infanta Leonor Univ Hosp Dept Internal Med HIV Unit Madrid Spain Inst Salud Carlos III Ctr Invest Biomed Red Enfermedades Infecciosas CIB Madrid 28222 Spain Hosp 12 Octubre imas12 Biomed Res Inst Imas12 Internal Med Dept Res Inst Madrid Spain La Paz Univ Hosp Internal Med Dept Infect Dis Unit Madrid Spain La Princesa Univ Hosp Hosp Princesa Dept Internal Med & Infect Dis Madrid 28006 Spain Hosp Ramos Mejia Liver Unit C1221ADC Buenos Aires Argentina Inst Salud Carlos III Viral Hepatitis Reference & Res Lab Ctr Nacl Microbiol Madrid 28222 Spain

Extracellular vesicles (EVs) are an increasingly promising tool for liquid biopsy in liver diseases. Hepatitis C Virus (HCV) infection, alone or together with Human Immunodeficiency Virus (HIV) infection significantly impacts on the microRNA (miRNA) EVs content resembling chronic hepatitis C (CHC) progression. The objective of the study was to delve into the intricate EVs-miRNA profiles in CHC patients with different liver fibrosis stages, aiming to pinpoint non-invasive markers capable of distinguishing significant fibrosis. Plasma EV-miRNAs from 50 CHC patients (HCV+ and HCV+/HIV+) stratified in no significant (F < 2) and significant (F >= 2) fibrosis, were massively sequenced. General linear models (GLM) were used to identify significantly differential expressed (SDE) miRNAs according to liver fibrosis stages (F >= 2 and F < 2). Dysregulated biological pathways were subsequently analyzed in silico for the following groups: i) all patients;ii) HCV+;and iii) HCV+/HIV+. Multiple-ordered logistic regression analysis was performed to develop a score to identify F >= 2 cases. The diagnostic potential of both the SDE miRNAs and the developed score was assessed using ROC curve analysis. With respect to all CHC patients, two SDE miRNAs (hsa-miR-122-5p and hsa-miR-92a-3p) were identified which regulate genes related to cytoskeleton organization. Regarding their diagnostic performance to discriminate F >= 2, both miRNAs individually demonstrated acceptable diagnostic values. However, their combined use in a new score enhanced their diagnostic performance (AUROC = 0.833). In the HCV+ subgroup, 8 SDE miRNAs (hsa-miR-122-5p, hsa-miR-320c, hsa-miR-3615, hsa-miR-320a-3p, hsa-miR-374b-5p, hsa-let-7a-3p, hsa-miR-199a-5p, hsa-miR-142-5p), which regulate macrophage activity and cell growth/death regulation, were recognized. Among them, hsa-miR-3615 displayed the highest diagnostic performance to discriminate F >= 2 (AUROC = 0.936). With respect to HCV+/HIV+, 18 SDE miRNAs (hsa-miR-4

关键词： Hepatitis C infections micrornas Extracellular vesicles Fibrosis Biomarkers

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Stem-Cell Derived Exosomal micrornas as Biomarkers and Therapeutics for Pediatric Cardiovascular Disease

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CURRENT TREATMENT OPTIONS IN CARDIOVASCULAR MEDICINE 2025年第1期27卷 1-10页

作者： Wasserman, Aaron H. Abolibdeh, Bana Hamdan, Reema Hong, Charles C. Michigan State Univ Coll Human Med Dept Med E Lansing MI 48823 USA Michigan State Hlth Sci Henry Ford Hlth Detroit MI 48808 USA

Purpose of ReviewIn recent years, several pre-clinical studies have demonstrated the therapeutic potential of stem cell-derived exosomes in the treatment of cardiovascular disease (CVD). Here, we evaluate their potential as biomarkers for the detection and monitoring of CVD, with a particular focus on pediatric heart *** FindingsExosomes isolated from stem cell sources, including mesenchymal stem cells (MSCs) and pluripotent stem cells (PSCs), benefit cardiovascular function, inflammatory responses, and angiogenesis in injured and diseased hearts. These exosomes carry a variety of cargo, such as proteins, lipids, and nucleic acids. However, the majority contain non-coding RNA *** of the existing literature for several non-coding RNAs and their relationship to CVD suggests that exosomes containing micrornas (miRNAs) can serve as promising biomarkers for CVD due to their presence in circulation, ease of isolation, and therapeutic potential. These biomarkers are especially promising as screening and diagnostic tools for the early detection of pediatric and congenital heart disease.

关键词： Cardiovascular Disease Congenital Heart Disease Mesenchymal Stem Cells micrornas Non-Coding RNAs Stem Cell-Derived Exosomes

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To be or not to be: navigating the influence of micrornas on cervical cancer cell death

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CANCER CELL INTERNATIONAL 2025年第1期25卷 1-23页

作者： Taghizadieh, Mohammad Kalantari, Masoumeh Bakhshali, Roksana Kobravi, Sepehr Khalilollah, Shayan Baghi, Hossein Bannazadeh Bayat, Mobina Nahand, Javid Sadri Akhavan-Sigari, Reza Tabriz Univ Med Sci Fac Med Dept Pathol Tabriz Iran Tehran Univ Hlth Sci Dept Biol Tehran Iran Omid Canc Ctr Ahvaz Iran Islamic Azad Univ Fac Dent Dept Oral & Maxillofacial Surg Tehran Med Sci Branch Tehran Iran Islamic Azad Univ Fac Med Dept Neurosurg Tehran Med Sci Tehran Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Univ Med Ctr Tuebingen Dept Neurosurg Tubingen Germany Coll Humanum Warsaw Management Univ Dept Hlth Care Management & Clin Res Warsaw Poland

With all diagnostic and therapeutic advances, such as surgery, radiation- and chemo-therapy, cervical cancer (CC) is still ranked fourth among the most frequent cancers in women globally. New biomarkers and therapeutic targets are warranted to be discovered for the early detection, treatment, and prognosis of CC. As component of the non-coding RNA's family, micrornas (miRNAs) participate in several cellular functions such as cell proliferation, gene expression, many signaling cascades, apoptosis, angiogenesis, etc. MiRNAs can suppress or induce programmed cell death (PCD) pathways by altering their regulatory genes. Besides, abnormal expression of miRNAs weakens or promotes various signaling pathways associated with PCD, resulting in the development of human diseases such as CC. For that reason, understanding the effects that miRNAs exert on the various modes of tumor PCD, and evaluating the potential of miRNAs to serve as targets for induction of cell death and reappearance of chemotherapy. The current study aims to define the effect that miRNAs exert on cell apoptosis, autophagy, pyroptosis, ferroptosis, and anoikis in cervical cancer to investigate possible targets for cervical cancer therapy. Manipulating the PCD pathways by miRNAs could be considered a primary therapeutic strategy for cervical cancer.

关键词： Cervical cancer micrornas Apoptosis Ferroptosis Pyroptosis Autophagy

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Persistent organic pollutants and plasma micrornas: A community-based profiling analysis

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ENVIRONMENT INTERNATIONAL 2025年 197卷 109328页

作者： Qu, Jingli Li, Wending Jia, Chengyong Jiang, Qin Tang, Rui Yin, Yu Wang, Xi Long, Pinpin Wu, Tangchun Yuan, Yu Huazhong Univ Sci & Technol Tongji Med Coll Dept Occupat & Environm Hlth Sch Publ HlthMinist EducKey Lab Environm & Hlth Wuhan 430030 Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Sch Publ Hlth State Key Lab Environm Hlth Incubating Wuhan 430030 Peoples R China Columbia Univ Mailman Sch Publ Hlth Dept Environm Hlth Sci New York NY 10032 USA

Background: Whether exposure to persistent organic pollutants (POPs) may incur micrornas (miRNAs) dysregulation remains largely unclear. Objectives: We aim to identify the miRNA signature and related pathways of low-level POPs exposure in a community-based population. Methods: We used general linear regression to model the association of POPs with plasma miRNAs, adjusting for age, gender, smoking, alcohol consumption, body mass index, triglyceride, and total cholesterol levels. We performed pathway enrichment analysis based on 11 experimentally validated and prediction-based databases, and performed tissue specificity analysis. Results: We identified 19 POPs significantly associated with 23 miRNAs at false discovery rate-adjusted P value < 0.2, most of which were related to organophosphorus and organochlorine pesticides. Pathway enrichment of the associated miRNAs highlighted chromosome segregation, RNA splicing, autophagy regulation, lipid metabolism, cell growth, development and differentiation, cell cycle regulation, neural network construction, and signal transduction. Notably, 13 POPs were positively associated with miR-6810-3p, a miRNA enriched in temporal lobe with high tissue specificity (Tissue Specificity Index = 0.78). Pathway analysis revealed that miR-6810-3p contributes to the positive regulation of autophagy and multiple cellular functions related to the nervous system such as transport along microtubules, maintenance of cell polarity, and synaptic transmission. Conclusion: In conclusion, we identified POPs-related miRNA signatures in community-dwelling adults, and highlighted miR-6810-3p in association with multiple POPs, with a potential role in nervous system regulation.

关键词： Persistent organic pollutants micrornas Pathway enrichment Gene ontology enrichment analysis Neurological function

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Evaluating micrornas as diagnostic tools for lymph node metastasis in breast cancer: Findings from a systematic review and meta-analysis

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CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY 2025年 207卷 104598-104598页

作者： Martinez, Coral Gonzalez Therapontos, Stavros Lorente, Jose A. Lucena, Miriam Alcaide Ortega, F. Gabriel Serrano, M. Jose Univ Granada GENYO Ctr Genom & Oncol Res Pfizer Andalusian Reg Govt PfizerAndalusian Reg GovtLiquid biopsy & Canc In Ave Ilustrac 114 Granada 11418016 Spain Biomed Res Inst IBS Granada Avda Madrid 15 Granada 18012 Spain Univ Granada Fac Med Legal Med & Toxicol Dept Lab Genet Identificat Ave Invest 11 Granada 18071 Spain Univ Utrecht Heidelberglaan 8 NL-3584 CS Utrecht Netherlands Hosp Univ San Cecilio Serv Cirugia Gen & Aparato Digest Unidad Patol Mamaria Granada Spain Virgen de las Nieves Univ Hosp Integral Oncol Div Av Dr Oloriz 16 Granada 18012 Spain Univ Hosp Virgen Nieves Pathol Anat Unit Mol Pathol Lab Granada 18016 Spain

Lymph node metastasis (LNM) significantly affects the prognosis and clinical management of breast cancer (BC) patients. This systematic review and meta-analysis aim to identify micrornas (miRNAs) associated with LNM in BC and evaluate their potential diagnostic and prognostic value. Following PRISMA guidelines, a comprehensive literature search was conducted in PubMed, Web of Science, and SCOPUS databases, to assess the role of miRNAs in LNM BC. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the quality of included studies. A total of 84 miRNAs were identified as differentially expressed in BC patients with LNM. Of these, a meta-analysis was performed in two micrornas that were present in at least 3 different articles with a coherent expression direction: miR-155 and miR-34a. The meta-analysis returned a pooled a Log2 fold change of 1.50 for miR-155 (upregulated) and -0.53 for miR-34a (downregulated) with no evidence of publication bias, and a low risk of bias and applicability concerns. To conclude, this study names miR-155 and miR34a as potential diagnostic biomarkers for LNM in BC, although further experimental validation is necessary to confirm these findings and develop non-invasive diagnostic tools for clinical use.

关键词： Breast cancer Lymph node metastasis micrornas MiR-155 MiR-34a Systematic review Meta-analysis

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Host micrornas as regulators of porcine reproductive and respiratory syndrome virus infection

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VIROLOGY 2025年 603卷 110361-110361页

作者： Guo, Shu-yuan Feng, Wen-hai China Agr Univ Coll Biol Sci Frontiers Sci Ctr Mol Design Breeding Beijing 100193 Peoples R China China Agr Univ Coll Biol Sci State Key Lab Anim Biotech Breeding Beijing 100193 Peoples R China China Agr Univ Coll Biol Sci Minist Agr Key Lab Soil Microbiol Beijing 100193 Peoples R China China Agr Univ Coll Biol Sci Dept Microbiol & Immunol Beijing 100193 Peoples R China

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a significant pathogen in the swine industry. micrornas (miRNAs), a class of small non-coding RNA molecules, have risen to prominence as key regulators of gene expression at the post-transcriptional level. Their significance in regulating virus-host interactions is now widely acknowledged. So far, more than 30 miRNAs have been found to play a role in PRRSV infection. They can regulate viral genome stability and protein synthesis by targeting PRRSV RNA, and modulate the host immune response, thus affecting PRRSV replication. Understanding the role of miRNAs in PRRSV infection can further elucidate the pathogenesis of PRRSV and pave the way for the development of new antiviral strategies through miRNA-based therapies. This review will focus on how host miRNAs alter PRRSV infection, underscoring their multifaceted involvement in the interplay between virus and host.

关键词： PRRSV micrornas Infection Immune response Antiviral strategy

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Vitamin D modulates the content of inflammatory micrornas in extracellular vesicles from human adipocyte cells in inflammatory context

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BIOFACTORS 2025年第1期51卷 e70003页

作者： Payet, Thomas Astier, Julien Bournot, Lorrine Sicard, Flavie Robert, Stephane Lacroix, Romaric Wabitsch, Martin Landrier, Jean-Francois Mounien, Lourdes Aix Marseille Univ INSERM INRAE C2VN Marseille France Biomeostasis CRO Nutr Behav & Metab Disorders La Penne Sur Huveaune France PhenoMARS Aix Marseille Technol Platform CriBiom Marseille France Biogenopole Dept Haematol CHU Timone AP HM Marseille France Ulm Univ Med Ctr Dept Pediat & Adolescent Med Ulm Germany

Inflammation of adipose tissue is a contributing factor to many chronic diseases associated with obesity. We previously showed that micronutrients such as vitamin D (VD) limited this metabolic inflammation by decreasing inflammatory markers expression including miR-155 (microRNA-155) or miR-146a in different in vitro and in vivo models. These miRNAs could be incorporated into extracellular vesicles (EVs) in order to modulate the activity of target cells. Nevertheless, the role of VD on the miRNAs contained in EVs from adipose tissue in inflammatory conditions remains unclear. In this study, we used a human model of SGBS (Simpson-Golabi-Behmel syndrome) adipocytes preincubated with 1,25(OH)2D (the active form of VD) before an inflammatory stress with tumor necrosis factor alpha (TNF alpha). First, we confirmed by quantitative PCR that the expression of classical inflammatory factors (TNF alpha and chemokine ligand 2 [CCL2/MCP1]), miR-146a, and miR-155 was increased significantly under inflammatory conditions in SGBS cells and that VD prevented this up-regulation. Secondly, transmission electron microscope imaging of EVs preparations in supernatant allowed visualization of small and large vesicles under these conditions. Then, EVs were obtained with isolation kit and the expression of miR-155 and miR-146a were measured. The expression of miR-155 under TNF alpha effect was increased in EVs while miR-146a was not detected. Moreover, we also showed that the TNF alpha-mediated expression of miR-155 in EVs was significantly reduced by a VD pre-incubation of cells. Using miRNA PCR array, we also identified 33 miRNAs, organized in 5 clusters that were differentially regulated by TNF alpha and VD. Bioinformatic analysis of biological pathways revealed that the different miRNAs targeting genes that are involved in important cell process such as the regulation of transcription or protein phosphorylation. In conclusion, these results support for the first time that VD modulated

关键词： Vitamin D extracellular vesicles inflammation human adipocyte micrornas

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Circulating micrornas: A remarkable opportunity as non-invasive biomarkers from adult to pediatric brain tumor patients

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CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY 2025年 208卷 104650-104650页

作者： D'Antonio, Federica Spinello, Zaira Bargiacchi, Lavinia Splendiani, Elena Rossi, Sabrina Masuelli, Laura Mastronuzzi, Angela Locatelli, Franco Ferretti, Elisabetta Catanzaro, Giuseppina Sapienza Univ Rome Dept Expt Med I-00161 Rome Italy Bambino Gesu Children Hosp Dept Haematol Oncol & Cell & Gene Therapy IRCCS Rome Italy Sant Andrea Univ Hosp Morphol & Mol Pathol Unit I-00189 Rome Italy Bambino Gesu Childrens Hosp IRCCS Pathol Unit Rome Italy Link Campus Univ Dept Life Sci Hlth & Hlth Profess I-00165 Rome Italy

Central nervous system (CNS) tumors represent the most frequent solid tumors among adolescents and children, and the leading cause of cancer-related death in men < 40 and women < 20 years of age. Brain tumors are challenging to diagnose, monitor, and treat. The current diagnostic approach involves magnetic resonance imaging (MRI), tumor histology, molecular characterization and cytologic analysis of cerebrospinal fluid (CSF). However, surgical procedures pose potential risks to the patient's health, not achieving good accuracy. For these reasons, it is crucial to identify new non-invasive disease biomarkers to improve patients' stratification at diagnosis and during follow-up and prognosis. micrornas (miRNAs) are a class of short RNA molecules that have been demonstrated in numerous studies to be dysregulated in brain tumor patients. As a result, they may be used as biomarkers of brain tumors. Additionally, miRNAs can be analyzed in liquid biopsy samples, such as blood and CSF, providing a non-invasive source of biomolecular data on patients' disease status. This review aims to highlight the role of miRNAs in liquid biopsy, also known as circulating miRNAs, as potential non-invasive cancer biomarkers in both adult and pediatric populations and to suggest their potential impact on clinical trials.

关键词： micrornas Circulating micrornas Liquid biopsy Pediatric brain tumors Adult brain tumors Biomarkers

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