microRNA

Overview

MicroRNAs (miRNAs) are short, non-coding RNA molecules, typically about 22 nucleotides long, that regulate gene expression at the post-transcriptional level. They are transcribed as longer primary hairpin transcripts, processed in the nucleus and cytoplasm into mature duplexes, and loaded into the RNA-induced silencing complex. There, the guide strand directs the complex to partially complementary sequences in the 3′ untranslated regions of target messenger RNAs, causing translational repression or transcript destabilization. Because base pairing is imperfect, a single miRNA can suppress many transcripts and a single transcript can be tuned by many miRNAs, placing miRNAs at the center of regulatory networks governing differentiation, proliferation, apoptosis, metabolism, cellular senescence, and immune signaling. Individual family members such as MIR21 act on defined pathway components, and miRNA activity intersects with signaling axes including Transforming growth factor beta (TGF-β) and Wnt/β-catenin.

In biomedical research, miRNAs are studied both as disease biomarkers and as therapeutic targets. Altered miRNA expression accompanies cancer, cardiovascular disease, inflammatory and fibrotic conditions, and neurodegeneration, and miRNAs are also carried by extracellular vesicles and extracellular exosomes, which shield them from plasma nucleases and allow them to act in intercellular communication. This stability makes circulating miRNAs attractive analytes for minimally invasive liquid biopsy in blood, plasma, serum, cerebrospinal fluid, and other biofluids, alongside markers such as cell-free tumour DNA, and for applications ranging from cancer screening and treatment monitoring to studies of aging. Because miRNAs are present at low abundance and are closely related in sequence, detection typically relies on quantitative PCR, sequencing, or amplified biosensing strategies — including CRISPR-Cas methods built on CRISPR-Cas12a combined with isothermal amplification schemes such as catalytic hairpin assembly and hybridization chain reaction. On the therapeutic side, synthetic mimics and antisense inhibitors delivered by lipid nanoparticle are being explored to restore or block specific miRNA activities.

Recent Publications Summary (latest 30 papers)

Recent publications demonstrate the emerging role of microRNAs (miRNAs) in extracellular vesicles, exosomes, and other extracellular particles as promising biomarkers for disease diagnosis, prognosis, and treatment monitoring across diverse clinical contexts. Studies isolated and characterized miRNA profiles from tissue interstitial fluid, plasma, nipple discharge, and cerebrospinal fluid in multiple diseases, establishing that EV-derived miRNA signatures offer tissue-specific and disease-relevant diagnostic information 42546027Aug42307695Jun. Dysregulated miRNA panels have been identified in Parkinson's disease 42541533Aug, acute lymphoblastic leukemia 42340965Jun, breast cancer 42306980Jun42213364May, pancreatic cancer 42081539May, urothelial carcinoma in hemodialysis patients 42374859Jun, idiopathic intracranial hypertension 42308437Jun, coronary artery disease 42162444May, equine piroplasmosis 42066974May, and bladder cancer 41933678Apr. The abundance and composition of circulating miRNAs vary with aging 42319614Jun and clinical disease state, positioning them as accessible, noninvasive alternatives to invasive procedures for early detection and disease monitoring, with applications extending to predicting treatment response in bariatric surgery candidates 42140861May and monitoring chemoradiotherapy efficacy in rectal cancer 42011875Apr.

Emerging detection technologies have substantially advanced miRNA quantification capabilities and enabled sensitive, multiplexed analysis. Novel biosensing platforms integrating CRISPR/Cas12a with catalytic hairpin assembly or hybridization chain reaction achieved detection limits as low as 2 fM and 37 fM, respectively, enabling ultrasensitive and single-base-discriminant miRNA detection 42424186Jul42417866Jul. Weight-controllable biobarcode probes enabled multi-input analysis of three miRNA targets for breast cancer classification with 84% accuracy on clinical serum samples 42306980Jun. Electrochemical biosensors successfully quantified multiple miRNAs encapsulated in lipid nanoparticle with high selectivity 42037292Apr, and a tri-modal CRISPR/Cas12a system provided colorimetric, fluorescent, and electrochemical outputs for simultaneous tumor marker verification 41935002Apr. Additionally, tangential flow filtration was optimized for scalable isolation of exomeres, a class of nanoscale particles enriched in RNAi proteins, which preferentially deliver miRNAs to target cells more effectively than conventional extracellular vesicles 42370700Jun. Microarray-based profiling identified time-sensitive miRNAs as quality indicators for serum samples, highlighting critical preanalytical factors affecting miRNA measurement reliability 42246163Jun.

miRNA dysregulation participates in complex regulatory networks that modulate pathophysiology across multiple diseases. In moyamoya disease, patient-derived plasma extracellular vesicles and induced pluripotent stem cell-derived endothelial cells showed depleted angiogenesis-related miRNAs; treatment with mesenchymal stem cell-derived extracellular vesicles restored these depleted miRNAs and rescued angiogenic function 42274939Jun. Competing endogenous RNA networks revealed that mesothelioma tumors with favorable immunotherapy responses exhibited overexpressed miRNAs targeting networks linked to immune suppression 42177870May. MicroRNA networks controlling the WNT pathway and senescence-associated secretory phenotype were implicated in skeletal aging, with miR-183-5p upregulation and miR-135a-5p/miR-671-5p downregulation as common signatures across aging models and radiation-induced acceleration 42183846May. In chronic myeloid leukemia, imatinib induced time-dependent transcript and miRNA alterations through the Hippo-YAP pathway 42201499May.

Therapeutic strategies increasingly harness miRNA regulation for disease treatment and modulation of cellular states. Traditional Chinese medicine (Renshen Decoction) improved myocardial energy metabolism and attenuated ventricular remodeling in heart failure by regulating exosomal miR-30e-5p-mediated intercellular communication between cardiac fibroblasts and cardiomyocytes 42214224May. A microRNA-governed autocatalytic Fenton nanoplatform enabled miRNA-regulated intratumoral chemistry and cell-selective cancer imaging by deploying miRNA-activatable DNAzymes to silence catalase mRNA and induce cytotoxic hydrogen peroxide accumulation 42017828Apr. Ribozyme-scaffolded, miRNA-sensing CRISPR systems detected epithelial-to-mesenchymal transition through EMT-specific miRNA signatures and directed Cas9 effectors to selectively eliminate mesenchymal cells and filter cell populations 41950922Apr. Engineered extracellular vesicles delivering metabolic miRNAs, enzymes, and redox modulators are being integrated with CRISPR-based metabolic engineering to enhance mitochondrial biogenesis and improve the maturation of induced pluripotent stem cell-derived cardiomyocytes for cardiac regeneration 41897402Mar. Interleukin-11-regulated miRNAs were investigated as both functional mediators and circulating biomarkers of cardiac fibrosis, with therapeutic targeting potential 41841256Mar.

What Changes, What Holds

1. Vesicle-carried miRNAs are being read out of compartments far beyond blood — REINFORCES — Interstitial fluid, nipple discharge, and CSF profiling extends the liquid-biopsy premise the Overview already states, and the disease list grows without the class of claim changing: dysregulated panels in another cancer or another neurodegenerative cohort are more instances, not a new kind of evidence 42546027Aug42541533Aug. The one genuinely load-bearing point is that signatures appear tissue-specific rather than merely disease-associated — that is what would justify moving from correlation to a deployable assay, and it is not yet demonstrated prospectively.

2. Detection now reaches femtomolar limits with single-base discrimination and multiplexed readout — METHOD — Cas12a coupled to catalytic hairpin assembly or hybridization chain reaction, named in the Overview as a strategy, has become a quantified capability: 2 fM sensitivity and discrimination between closely related family members addresses precisely the low-abundance, high-homology problem the baseline flags 42424186Jul42417866Jul. Set against this, preanalytical work identifying time-sensitive serum miRNAs implies assay sensitivity has outrun sample-handling reliability — the limiting error is now upstream of the sensor.

3. Exosomal miRNA depletion can be therapeutically reversed, making the profile a treatable lesion rather than a readout — NEW DIRECTION — Restoring angiogenic miRNAs in moyamoya endothelial cells with donor vesicles recasts circulating miRNA content as an intervention target in its own right, whereas the Overview frames extracellular miRNAs as cargo for communication and as analytes 42274939Jun. Network findings in senescence and WNT control sharpen axes the baseline already names; the imatinib–Hippo-YAP result adds a drug-induced remodeling mode the baseline does not cover 42183846May.

4. miRNA state can be used as a computational input that directs a cytotoxic effector — NEW DIRECTION — Ribozyme-scaffolded sensors and DNAzyme-Fenton platforms use endogenous miRNA signatures as the trigger condition for Cas9 killing or intratumoral chemistry, inverting the therapeutic logic in the Overview, where mimics and inhibitors are the payload and miRNA the thing modulated 41950922Apr42017828Apr. Here the miRNA is the sensor and something else does the damage. All of it is preclinical; specificity depends on signature thresholds that no in vivo work has yet calibrated.

Overview update candidates: femtomolar; single-base-discriminant Cas12a detection; miRNA-triggered effector systems as a therapeutic modality distinct from mimics and inhibitors.