Emerging concepts of miRNA therapeutics: from cells to clinic

Trends in Genetics, Год журнала: 2022, Номер 38(6), С. 613 - 626

Опубликована: Март 15, 2022

Single microRNAs (miRNAs) regulate large subsets of mRNA targets. Although this property makes miRNAs potentially a powerful therapeutic tool, it also represents major challenge in terms controlling adverse effects that have been observed clinical trials.Besides systemic applications via injection and infusion, advanced strategies emerge for miRNA-based drug administration implantable 3D matrices, inhalation schemes, intake food.A combination miRNA therapeutics with chemical modifications, biomolecule conjugation, or the use carriers improves site-directed efficient cell targeting.A comprehensive risk assessment is required before any vivo targeting to minimize off-target avoid overdosing miRNAs. MicroRNAs are very genetic regulators, as evidenced by fact single can direct entire cellular pathways interacting broad spectrum target genes. This renders highly interesting tools restore functions altered part disease phenotype. However, strength weakness because their so numerous hardly be avoided. In review, we point out main challenges specifically address problems need surmounted push toward application Particular emphasis given approaches already found way into studies. What promises therapeutics?miRNAs (see Glossary) small, noncoding RNAs serve post-transcriptional regulators protein encoding There more than 2300 different human cells time- tissue-dependent expression patterns [1.Alles J. et al.An estimate total number true miRNAs.Nucleic Acids Res. 2019; 47: 3353-3364Crossref PubMed Scopus (207) Google Scholar, 2.Kozomara A. al.miRBase: From microRNA sequences function.Nucleic D155-D162Crossref (1326) 3.Ludwig N. al.Distribution across tissues.Nucleic 2016; 44: 3865-3877Crossref (529) Scholar]. Essential aspects biogenesis its functionality provided Box 1. Criteria fidelity addressed below.Box 1Cellular biogenesismiRNA located exons introns protein-encoding genes intergenic regions. They coregulated together host under control own promoters [103.Olena A.F. Patton J.G. Genomic organization microRNAs.J. Cell. Physiol. 2010; 222: 540-545PubMed During (thoroughly reviewed elsewhere, e.g., 104.Ha M. Kim V.N. Regulation biogenesis.Nat. Rev. Mol. Cell Biol. 2014; 15: 509-524Crossref (3208) 105.Winter al.Many roads maturity: MicroRNA regulation.Nat. 2009; 11: 228-234Crossref (1970) Scholar]), transcribed RNA polymerase II III form primary (pri-miRNAs), which up several thousand nucleotides length shaped hairpin structure. pri-miRNAs further processed Drosha-DGCR8 microprocessor complex nucleus generate an precursor (pre-miRNA) approximately 70 length. noncanonical biogenesis, intron-encoded pre-miRNAs (mirtrons) directly along coencoded transcripts through spliceosomes. The pre-miRNA exported exportin-5 cytoplasm, where cleaved duplex 22 RNase Dicer double-stranded binding enzyme TRBP. strands subsequently incorporated RISC, allowing ribonucleoprotein bind usually within 3′ untranslated regions mRNAs. Reverse complementary takes place seed region, situated at 2 7 miRNA's 5′ end. results inhibition abrogation translation process. It estimated 60% all subject regulation [106.Friedman R.C. al.Most mammalian mRNAs conserved targets microRNAs.Genome 19: 92-105Crossref (6022) Scholar], making central signaling widespread impact on almost every biological process [6.Gebert L.F.R. MacRae I.J. function animals.Nat. 20: 21-37Crossref (893) Besides level, there recent evidence translocate transcription efficiency specific genes, enhancing networks [107.Liu H. al.Nuclear gene regulation, immunity cancer.Mol. Cancer. 2018; 17: 64Crossref (167) Scholar].Physiological changes pivotal consequence cascades. many scenarios, plays likewise role modifying pathological [4.Subramanian S. Steer C.J. Special issue: health disease.Genes (Basel). 10Crossref (10) diagnostic potential levels, these small offer themselves purposes targeted manipulation crucial phenotype [5.Huang W. MicroRNAs: Biomarkers, diagnostics, therapeutics.Methods 2017; 1617: 57-67Crossref (100) intervention most efficient, consequently especially attractive, regulated Thus, spite relatively moderate effect each shown miR-34a-5p has identified hub T Scholar,7.Hart al.miR-34a networks.J. Immunother. 7: 187Crossref (19) Vice versa, one pathway typically miRNAs, resulting regulatory network, addressing majority molecular pathomechanisms humans.Against background, not surprising that, according records, since 2015, 600 articles published heading 'miRNA-based therapeutics'. future undoubtedly appealing, still great practical difficulties overcome, including identification proper routes, in-body stability, tissues types, attaining intended intracellular effects. Hence, only few drugs have, now, entered test phase (Table 1). following sections, effective nonhazardous therapeutics. We particularly emphasize preclinical studies developed associated using therapeutics.Table 1Clinical trials therapeuticsaNCT numbered registered ClinicalTrials.gov; EudraCT EU Clinical Trials Register (clinicaltrialsregister.eu).miRNA nameTargeted miRNAMode actionBackground diseaseBody application/permission uptakeClinical trial number(s)RefsAMT-130bPhase I ongoing.Artificial miRNAamiRNA expressionHuntington diseaseStereotaxic infusion/viral transfer (adeno-associated vector)NCT04120493[23.Keskin al.AAV5-miHTT lowers huntingtin without patient-derived neuronal cultures astrocytes.Mol. Ther. Methods Clin. Dev. 275-284Abstract Full Text PDF (20) 24.Miniarikova al.Design, characterization, lead selection development therapy Huntington's disease.Mol. Nucleic Acids. 5e297Abstract (64) 25.Samaranch L. al.MR-guided parenchymal delivery adeno-associated viral vector serotype 5 non-human primate brain.Gene 24: 253-261Crossref (41) Scholar]RG-012/lademirsen/SAR339375cPhase ongoing.miR-21Anti-miRAlport syndromeSubcutaneous injection/chemical modification (phosphorothioate)NCT03373786, NCT02855268[70.Gomez I.G. al.Anti-microRNA-21 oligonucleotides prevent Alport nephropathy progression stimulating metabolic pathways.J. Invest. 2015; 125: 141-156Crossref (246) Scholar,76.Kelnar K. al.Quantification mimics whole blood from nonhuman primates.Anal. Chem. 86: 1534-1542Crossref (49) Scholar,122.Kashtan C.E. Gross O. practice recommendations diagnosis management syndrome children, adolescents, young adults – update 2020.Pediatr. Nephrol. 2021; 36: 711-719Crossref (14) Scholar,123.Kashtan Correction to: adults-an 731Crossref (2) Scholar]RG-125/AZD4076dPhase completed.miR-103/107Anti-miRNonalcoholic steatohepatitis (NASH) patients type diabetes/prediabetesSubcutaneous injection/biomolecule conjugation (GalNAc)NCT02612662, NCT02826525[76.Kelnar 77.Drenth J.P.H. Schattenberg J.M. nonalcoholic graveyard: Established hurdles planning success.Expert Opin. Investig. Drugs. 2020; 29: 1365-1375Crossref (16) 78.Huang Y. Preclinical advances GalNAc-decorated nucleic acid therapeutics.Mol. 6: 116-132Abstract (171) Scholar]MRG-110dPhase completed.miR-92aAnti-miRWoundsSkin (LNA)NCT03603431[124.Gallant-Behm C.L. al.A synthetic microRNA-92a inhibitor (MRG-110) accelerates angiogenesis wound healing diabetic nondiabetic wounds.Wound Repair Regen. 26: 311-323Crossref (46) Scholar,125.Abplanalp W.T. al.Efficiency derepression anti-miR-92a: Results first study.Nucleic Acid 30: 335-345Crossref (32) Scholar]MesomiR 1dPhase completed.miR-16miRNA mimicMalignant pleural mesothelioma, non–small lung cancerIntravenously/vehicle (nonliving minicells)NCT02369198[56.Reid G. al.Clinical TargomiRs, mimic-based treatment recurrent thoracic cancer.Epigenomics. 8: 1079-1085Crossref (120) Scholar,57.van Zandwijk al.Safety activity microRNA-loaded minicells malignant mesothelioma: A first-in-man, 1, open-label, dose-escalation study.Lancet Oncol. 18: 1386-1396Abstract (316) Scholar,126.Reid al.Restoring miR-16: novel approach mesothelioma.Ann. 2013; 3128-3135Abstract (158) Scholar]CDR132LdPhase completed.miR-132Anti-miRHeart failureIntravenously/chemical (LNA)NCT04045405[127.Taubel al.Novel antisense microRNA-132 heart failure: first-in-human 1b randomized, double-blind, placebo-controlled study.Eur. Heart 42: 178-188Crossref (47) Scholar,128.Batkai al.CDR132L systolic diastolic animal model chronic failure.Eur. 192-201Crossref (22) Scholar]Remlarsen/MRG-201ePhase completed.miR-29miRNA mimicKeloid disorderSkin (cholesterol)NCT02603224, NCT03601052[73.Gallant-Behm microRNA-29 mimic (remlarsen) represses extracellular matrix fibroplasia skin.J. Dermatol. 139: 1073-1081Abstract (74) Scholar,103.Olena Scholar,104.Ha Scholar]Miravirsen/SPC3649ePhase completed., fUnknown status.miR-122Anti-miRChronic hepatitis C virusSubcutaneous (LNA)NCT02508090, NCT02452814, NCT01200420, NCT01872936, NCT01727934, NCT01646489[16.Ottosen al.In vitro antiviral resistance profile miravirsen, anti-hepatitis virus factor miR-122.Antimicrob. Agents Chemother. 59: 599-608Crossref (130) Scholar,129.Gebert L.F. al.Miravirsen (SPC3649) inhibit miR-122.Nucleic 609-621Crossref (228) 130.Elmen al.LNA-mediated silencing primates.Nature. 2008; 452: 896-899Crossref (1381) 131.Lanford R.E. al.Therapeutic microRNA-122 primates infection.Science. 327: 198-201Crossref (1427) 132.Janssen H.L. al.Treatment HCV infection microRNA.N. Engl. Med. 368: 1685-1694Crossref (1644) Scholar]MRX34gStopped/terminated.miR-34amiRNA mimicSolid tumors (e.g., hepatocellular carcinoma), melanomaIntravenously/vehicle (liposomal)NCT01829971, NCT02862145[29.Beg M.S. al.Phase study MRX34, liposomal miR-34a mimic, administered twice weekly solid tumors.Investig. New 35: 180-188Crossref (468) Scholar,32.Daige al.Systemic miR34a liver Cancer 13: 2352-2360Crossref (112) Scholar,133.Huang H.Y. al.miRTarBase 2020: Updates experimentally validated microRNA-target interaction database.Nucleic 48: D148-D154PubMed Scholar]RG-101gStopped/terminated.miR-122Anti-miRChronic (GalNAc)EudraCT numbers 2015-001535-21, 2015-004702-42, 2016-002069-77[76.Kelnar Scholar,79.van der Ree M.H. al.Safety, tolerability, RG-101 C: 1B, randomised controlled trial.Lancet. 389: 709-717Abstract (143) Scholar,80.Stelma F. al.Immune natural killer who received dose anti-microRNA-122, RG-101.Hepatology. 66: 57-68Crossref (23) Scholar]Cobomarsen/MRG-106gStopped/terminated.miR-155Anti-miRMycosis fungoidesIntravenously/chemical (LNA)NCT02580552, NCT03713320, NCT03837457[134.Seto A.G. al.Cobomarsen, oligonucleotide miR-155, co-ordinately regulates multiple survival reduce proliferation cutaneous T-cell lymphoma.Br. Haematol. 183: 428-444Crossref (126) 135.James A.M. al.SOLAR: 2, global, active comparator investigate efficacy safety cobomarsen subjects mycosis fungoides (MF) [abstract].Hematol. 37: 562-563Crossref 136.Querfeld C. al.Preliminary 1 evaluating MRG-106, antagonist (LNA antimiR) microRNA-155, CTCL.Blood. 128: 1829Crossref Scholar]a NCT (clinicaltrialsregister.eu).b Phase ongoing.c ongoing.d completed.e completed.f Unknown status.g Stopped/terminated. Open table new tab How modify expression?The general aim ideally reverse changes. includes enhancement reconstitution endogenous act suppressors expressional reduction functional blocking drivers. To acids commonly used (Figure 1), (miRNA mimics), recombinant vectors carrying sequences, oligonucleotide-based inhibitors (anti-miRs) [8.van Rooij E. Kauppinen Development coming age.EMBO 851-864Crossref (433) Scholar].One currently pursued permeable molecules. These molecules exert by, example, proteins involved miRNA-specific secondary structures [9.Fan R. al.Small big roles biology microRNA-targeted therapeutics.RNA 16: 707-718Crossref Small designed aid bioinformatics experimental screening pharmacologically compounds [10.Disney M.D. al.Inforna 2.0: platform sequence-based design structured RNAs.ACS 1720-1728Crossref (95) Scholar,11.Suresh B.M. fragment-based identify optimize bioactive ligands RNA.Proc. Natl. Acad. Sci. U. 117: 33197-33203Crossref (0) example oncogenic miR-21. was target-oriented various low-molecular-weight [11.Suresh Natural rich source interfering [12.Alnuqaydan Targeting micro-RNAs products: strategy combat cancer.Am. Transl. 12: 3531-3556PubMed Curcumin has, breast cancer growth [13.Norouzi al.Curcumin adjunct modulator cancer.Curr. Pharm. Des. 171-177Crossref (35) Scholar].A combine treatments conventional drugs. drug-based therapies improved interventions pathways, affect outcomes [14.Seo H.A. al.MicroRNA-based combinatorial therapy: Effects anti-cancer therapies.Cells. 9: 29Crossref Liver-specific miR-122 considered driver (HCV) maintenance hepatocytes [15.Panigrahi al.miR-122 affects both initiation infections.J. Virol. 96e0190321PubMed (ClinicalTrials.gov identifiers NCT01872936), against counteracted combining miravirsen/SPC3649 [16.Ottosen Combined schemas chemotherapeutics manipulators being improvement antitumor therapies, common cancers such [17.Gong al.Functional exosome-mediated co-delivery doxorubicin hydrophobically modified 159 triple-negative therapy.J. Nanobiotechnol. 93Crossref (93) Scholar,18.Saatci al.Targeting lysyl oxidase (LOX) overcomes chemotherapy triple negative cancer.Nat. Commun. 2416Crossref (62) Scholar].The combined siRNAs offers another route improve constitute group conceived [19.Lam J.K. al.siRNA versus silencing.Mol. 4e252Abstract (465) establishment siRNA [20.Zhang al.The risks therapeutics: perspective.Drug Devel. 721-733Crossref (40) achieved coexpression plasmid, recently [21.Petrek al.Bioengineering long molecule carries RNAs.Appl. Microbiol. Biotechnol. 103: 6107-6117Crossref (13) Scholar].Artificially constructs, referred 'amiRNAs,' promise advancement amiRNAs combinations scaffolds transcripts. While show high specificity, siRNA-based design, processing ensured structure [22.Kotowska-Zimmer al.Artificial tools: Challenges opportunities.Wiley Interdiscip. RNA. 12e1640Crossref (3) An amiRNA-based (AMT-130) sequence Huntingtin pri-miR-451 scaffold employed identifier NCT04120493) [23.Keskin Scholar].miRNA sponges option manipulate levels constructs harboring sites. sequestration effectiveness sponges, circular RNAs, analyzed artificially sponge, six alternating sites miR-132 miR-212, tested, mouse models cardiovascular diseases [26.Lavenniah al.Engineered attenuate pressure overload-induced cardiac hypertrophy.Mol. 28: 1506-1517Abstract (45) Additional highlight naturally occurring therapeutically usable sponges. Recently, hsa_circ_0120472, two predicted sites, sponge miR-550a [27.Meng al.Circular circCCDC85A inhibits acting miR-550a-5p enhance MOB1A expression.Breast 2022; 1Crossref yet increasing will certainly promote approaches.What severe side therapeutics?Depending chosen warrant delivery, necessarily restricted tissue but cause prominent occurrence disastrous mimic. MRX34 tumor NCT01829971), hematologic malignancies, had terminated prematurely immune-related causing death four [28.Hong D.S. tumours.Br. 122: 1630-1637Crossref (183) Scholar,29.Beg make properties suppressor [30.Saito al.microRNA-34a agent cancer.J. 4: 1951-1959Crossref systemically amphoteric (i.e., pH-dependent) strategy, supposed take low-pH environment tumorous [31.Bouchie First enters clinic.Nat. 31: 577Crossref Animal models, however, showed uptake bone marrow spleen [32.Daige Scholar,33.Kelnar Bader qRT-PCR method determining biodistribution mimic.Methods 1317: 125-133Crossref (11) known generation preservation immune cells. Accordingly, context testing, dose-dependent modulation white now evident impacts cells, regulating calcium chemokine [3

Язык: Английский

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miRNA: A Promising Therapeutic Target in Cancer

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(19), С. 11502 - 11502

Опубликована: Сен. 29, 2022

microRNAs are small non-coding RNAs that regulate several genes post-transcriptionally by complementarity pairing. Since discovery, they have been reported to be involved in a variety of biological functions and pathologies including cancer. In cancer, can act as tumor suppressor or oncomiR depending on the cell type. Studies shown miRNA-based therapy, either inhibiting an inducing suppressor, is effective cancer treatment. This review focusses role miRNA therapeutic approaches with miRNAs how effectively delivered into system. We also summarized patents clinical trials progress for therapy.

Язык: Английский

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RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies

Journal of Pharmacology and Experimental Therapeutics, Год журнала: 2022, Номер 384(1), С. 133 - 154

Опубликована: Июнь 9, 2022

RNA interference (RNAi) provides researchers with a versatile means to modulate target gene expression. The major forms of RNAi molecules, genome-derived microRNAs (miRNAs) and exogenous small interfering RNAs (siRNAs), converge into RNA-induced silencing complexes achieve posttranscriptional regulation. has proven be an adaptable powerful therapeutic strategy where advancements in chemistry pharmaceutics continue bring RNAi-based drugs the clinic. With four siRNA medications already approved by US Food Drug Administration (FDA), several therapeutics advance clinical trials functions that closely resemble their endogenous counterparts. Although intended enhance stability improve efficacy, chemical modifications may increase risk off-target effects altering structure, folding, biologic activity away from natural equivalents. Novel technologies development today seek use intact cells yield true agents better represent structures, stabilities, activities, safety profiles molecules. In this review, we provide examination mechanisms action miRNAs siRNAs, physiologic pharmacokinetic barriers delivery, summary delivery platforms use. We overview pharmacology FDA-approved (patisiran, givosiran, lumasiran, inclisiran) as well five siRNAs miRNA-based currently trials. Furthermore, discuss direct expression stable carrier-based, vivo production novel for research development. SIGNIFICANCE STATEMENT: our summarize concepts (RNAi), molecular mechanisms, current state challenges drug focus discussion on Administration-approved those entered investigations. approaches producing new biological molecules are highlighted.

Язык: Английский

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Trials and Tribulations of MicroRNA Therapeutics

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1469 - 1469

Опубликована: Янв. 25, 2024

The discovery of the link between microRNAs (miRNAs) and a myriad human diseases, particularly various cancer types, has generated significant interest in exploring their potential as novel class drugs. This led to substantial investments interdisciplinary research fields such biology, chemistry, medical science for development miRNA-based therapies. Furthermore, recent global success SARS-CoV-2 mRNA vaccines against COVID-19 pandemic further revitalized RNA-based immunotherapies, including approaches treatment. Consequently, RNA therapeutics have emerged highly adaptable modular options therapy. Moreover, advancements chemistry delivery methods been pivotal shaping landscape immunotherapy, approaches. biotechnology pharmaceutical industry witnessed resurgence incorporating immunotherapies miRNA into programs. Despite progress preclinical research, field remains its early stages, with only few progressing clinical development, none reaching phase III trials or being approved by US Food Drug Administration (FDA), several facing termination due toxicity issues. These setbacks highlight existing challenges that must be addressed broad application therapeutics. Key include establishing sensitivity, specificity, selectivity towards intended targets, mitigating immunogenic reactions off-target effects, developing enhanced targeted delivery, determining optimal dosing therapeutic efficacy while minimizing side effects. Additionally, limited understanding precise functions miRNAs limits utilization. viable treatment, they technically economically feasible widespread adoption As result, thorough risk evaluation is crucial minimize prevent overdosing, address other Nevertheless, diseases evident, future investigations are essential determine applicability settings.

Язык: Английский

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Cancer immunotherapy: Challenges and limitations

Pathology - Research and Practice, Год журнала: 2021, Номер 229, С. 153723 - 153723

Опубликована: Ноя. 28, 2021

Язык: Английский

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The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Янв. 23, 2023

Abstract MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression by targeting mRNA. Moreover, it has been shown miRNAs changed in various diseases, such as cancers, autoimmune disease, infectious and neurodegenerative Diseases. The suppression miRNA function can be easily attained utilizing anti-miRNAs. In contrast, an enhancement achieved through the utilization modified mimetics. discovery appropriate carriers body become interesting subject for investigators. Exosomes (EXOs) therapeutic efficiency safety transferring different cellular biological components to recipient cell have attracted significant attention their capability carriers. Mesenchymal stem cells (MSCs) recognized generate wide range EXOs (MSC-EXOs), showing MSCs may effective EXO generation clinically measure compared other origins. MSC-EXOs widely investigated because immune attributes, tumor-homing flexible characteristics. this article, we summarized features MSC-EXOs, including production, purification, loading methods modification targeted delivery diseases. Graphical abstract

Язык: Английский

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Targeting miRNA by CRISPR/Cas in cancer: advantages and challenges

Military Medical Research, Год журнала: 2023, Номер 10(1)

Опубликована: Июль 17, 2023

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of sciences during the last decade. In study cancer, CRISPR/CRISPR-associated protein (Cas) system opens avenues into issues that were once unknown in our knowledge noncoding genome, tumor heterogeneity, precision medicines. CRISPR/Cas-based gene-editing technology now allows for precise permanent targeting mutations provides an opportunity target small non-coding RNAs such as microRNAs (miRNAs). However, development effective safe cancer gene editing therapy is highly dependent on proper design be innocuous normal cells prevent introducing other abnormalities. This aims highlight cutting-edge approaches cancer-gene based CRISPR/Cas miRNAs therapy. Furthermore, we potential challenges CRISPR/Cas-mediated miRNA offer advanced strategies overcome them.

Язык: Английский

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miRNAs: The Road from Bench to Bedside

Genes, Год журнала: 2023, Номер 14(2), С. 314 - 314

Опубликована: Янв. 25, 2023

miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised miRNA dysregulation reflects state and function of cells tissues, contributing to their dysfunction. The identification hundreds extracellular in biological fluids underscored potential field biomarker research. In addition, therapeutic is receiving increasing attention numerous conditions. On other hand, many operative problems including stability, delivery systems, bioavailability, still need be solved. this dynamic field, biopharmaceutical companies increasingly engaged, ongoing clinical trials point anti-miR miR-mimic molecules as an innovative class for upcoming applications. This article aims provide a comprehensive overview current knowledge on several pending issues new opportunities offered by treatment diseases early diagnostic tools next-generation medicine.

Язык: Английский

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Role of microRNAs in Immune Regulation with Translational and Clinical Applications

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1942 - 1942

Опубликована: Фев. 5, 2024

MicroRNAs (miRNAs) are 19-23 nucleotide long, evolutionarily conserved noncoding RNA molecules that regulate gene expression at the post-transcriptional level. In this review, involvement of miRNAs is summarized in differentiation and function immune cells, anti-infective responses, immunodeficiencies autoimmune diseases. Roles anticancer immunity transplantation solid organs hematopoietic stem cells also discussed. Major focus put on translational clinical applications miRNAs, including establishment noninvasive biomarkers for differential diagnosis prediction prognosis. Patient selection response to biological therapy one most promising fields application. Replacement or inhibition has enormous therapeutic potential, with constantly expanding possibilities. Although important challenges still await solutions, evaluation miRNA fingerprints may contribute an increasingly personalized management dysregulation a remarkable reduction toxicity treatment side effects. More detailed knowledge molecular effects physical exercise nutrition system facilitate self-tailored lifestyle recommendations advances prevention.

Язык: Английский

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The crosstalk between exosomal miRNA and ferroptosis: A narrative review

Biology of the Cell, Год журнала: 2025, Номер 117(1)

Опубликована: Янв. 1, 2025

Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive negative regulation it. For example, increased levels reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it not dependent on caspases, but iron. Exosomes are membrane-bound vesicles with size about 30 150 nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, proteins, which genetically similar their cells origin. found in all bodily fluids, blood, saliva, urine. Cells often release exosomes after fusion membrane. They play an important role immune cell-cell communication. miRNAs, noncoding RNAs length 18 24 nucleotides, involved regulating gene expression transcription. Emerging data suggests exosomal miRNAs implicated pathophysiological cells, metastasis, drug resistance, death. In addition, functional studies have indicated can key modulation by Therefore, this review, given importance ferroptosis, we decided elucidate relationship between diseases.

Язык: Английский

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