Updates on the role of miR-193b in the pathogenesis of human cancers and other diseases.

miR-193b has multifaceted roles in the pathogenesis of a wide spectrum of non-cancerous diseases. In fact, miR-193b does not have a single, unified function; rather, its role is highly context-dependent, acting as either a protective molecule or a pathogenic driver depending on the specific tissue and disease. As shown in Table 2 , human studies and cell line experiments show that miR-193b is a critical regulatory molecule involved in vascular diseases, metabolic disorders, inflammatory conditions, and neurodegeneration. Its expression is frequently dysregulated (either increased or decreased) in diseased tissues compared to healthy controls, and it exerts its effects by targeting key genes in pathways controlling cell proliferation, inflammation, metabolism, and matrix remodeling. Table 2 Summary of cell line/human studies on the role of miR-193b in non-malignant disorders. Table 2 Type of disorder Expression Pattern Samples Cell lines Pathway/Downstream targets Function Reference Systemic Sclerosis (SSc) Downregulated Skin biopsies and fibroblasts from SSc patients (n = 33; 5 diffuse, 28 limited) and healthy donors (n = 25) Human Pulmonary Artery Smooth Muscle Cells (HPASMCs) ↓ miR-193b → ↑ uPA → ↑ HPASMC Proliferation & ↓ Apoptosis → Proliferative Vasculopathy Promotes vascular smooth-muscle proliferation and survival, contributing to proliferative vasculopathy and intimal hyperplasia in SSc ( 53 ) Aortic Dissection (AD) Downregulated Thoracic aortic tissue from AD patients (n = 25) vs. normal aortic tissue from valve-replacement controls (n = 15) Human Aortic Smooth Muscle Cells (HASMCs) LncRNA H19 → ↓ miR-193b-3p → ↑ MMP-2, MMP-9 & ↓ α-SMA, SM22α → ↑ Proliferation & Migration of HASMCs Maintains vascular smooth-muscle contractility and aortic wall stability by repressing MMPs and supporting contractile proteins ( 54 ) Osteoarthritis (OA)/Cartilage Aging Upregulated with age Cartilaginous tissue from OA (n = 17), ACL injury (n = 3), and polydactylism (n = 6) Primary human chondrocytes ↑ miR-193b in aged/dedifferentiated chondrocytes Regulates COL2A1, aggrecan and SOX9 expression; may also target SOX5 Regulates ETV1 (ER81) and E2F6 ETV1 gives positive feedback on MMP1, MMP3 (stromelysin-1) and MMP13. E2F6 is involved in feedback on ADAMTS5 and TGF-β1. Promotes extracellular-matrix degradation, reduces matrix synthesis and may drive chondrocyte senescence/cartilage degeneration ( 55 ) Influenza A Virus (IAV) Infection Downregulated Not specified (cellular model) A549, HEK 293, HEK293T, Madin-Darby Canine Kidney (MDCK) epithelial cells miR-193b → ↓ β-catenin (CTNNB1) & LEF1 (Wnt/β-catenin pathway) → ↓ cyclin D1 → G0/G1 arrest → delayed vRNP nuclear import & suppressed IAV replication. Suppresses influenza A virus replication via inhibition of the Wnt/β-catenin pathway ( 56 ) Type 2 Diabetes (T2D) Upregulated Human plasma (113 cases, 113 controls) HepG2 ↑ miR-193b → ↓YWHAZ & ↓SOS2 ↓ YWHAZ → ↑ FOXO1 → ↑ PCK1 → ↑ Hepatic Glucose Production (Gluconeogenesis) ↓ SOS2 → ↑ Insulin Resistance → ↓ IR signaling & ↓ GLUT2 → ↓ Glucose Uptake Impairs glucose metabolism by enhancing hepatic gluconeogenesis and reducing glucose uptake; associated with increased diabetes risk. ( 57 ) Type 2 Diabetes (T2D) & Sarcopenia (Muscle Atrophy) Upregulated in serum and skeletal muscle Human Serum from 20 healthy controls (n = 20) vs. T2D (n = 20) C2C12 mouse myoblast ↑miR-193b → PDK1↓ → Akt/mTOR/S6K pathway inactivation → ↓Protein Synthesis & FOXO1 activation → ↑Atrogin-1 and MuRF1 → ↑Protein Degradation Impairs muscle growth by inhibiting protein synthesis and promoting degradation, leading to atrophy; inhibition attenuates muscle loss ( 58 ) Prediabetes/Impaired Glucose Tolerance (IGT) Upregulated Serum from 92 men: controls (n = 29), IFG (n = 22), IGT (n = 21), T2D (n = 20); validated in 2nd cohort: controls (n = 12), prediabetics (n = 6) Not investigated Not investigated Proposed diagnostic biomarker for prediabetic state; levels correlate with post-challenge glucose, triglycerides, and fatty liver index and Levels decrease upon therapeutic intervention ( 59 ) Psoriasis Downregulated Skin tissue (patients n = 6, controls n = 5) HaCaT, NHK ↓ miR-193b → ↑ ERBB4 protein → Activation of STAT3 & NF-κB pathways → Keratinocyte Hyperproliferation & Inflammatory Secretion Downregulation promotes keratinocyte proliferation and inflammatory-factor secretion ( 60 ) Parkinson's Disease (PD) Upregulated in PD patient PBMCs and chronic MPP + model; downregulated in acute MPP + model PBMCs from PD patients (n = 20) and age-matched controls (n = 20) SH-SY5Y neuroblastoma cells ↑ miR-193b → ↓ PGC-1α → ↓ FNDC5/BDNF & ↓ TFAM → ↓ Mitochondrial Biogenesis, ↑ Oxidative Stress, ↓ Neurotrophic Support → Neuronal Dysfunction and Apoptosis Inhibits neuroprotective pathways and promotes PD progression ( 61 ) Parkinson's Disease (PD) Downregulated in early PD; upregulated in late PD Human Brain Tissue (Frozen: Controls n = 25, Patients n = 53; FFPE: Controls n = 14, Patients n = 40) Human Cerebrospinal Fluid (Controls n = 22 Patients n = 41) SH-SY5Y neuroblastoma cells Late PD: ↑ miR-193b→ ↓ PGC-1α →↓ Mitochondrial biogenesis & antioxidant/anti-inflammatory responses (NFE2L2, SOD2, NOS1/2, IL1B) → Cellular stress, neuroinflammation & neuronal insulin signaling Key negative regulator of PGC-1α; upregulation in late PD impairs mitochondrial function and disrupts brain insulin signaling, linking metabolic and inflammatory dysfunction to neurodegeneration ( 62 ) Sepsis & Septic Shock Downregulated Discovery Phase: patients with sepsis (n = 6), septic shock (n = 6), controls (n = 3) Validation Phase: patients with sepsis (n = 30), septic shock (n = 30), controls (n = 30) Not investigated ↓ miR-193b → loss of repression → ↑ NFATC2, MAP2K7, CLDN2 → Hyperactivation of TCR signaling → Excessive inflammation Acts as an anti-inflammatory brake; its downregulation leads to immune hyperactivation and correlates inversely with CRP, PCT, IL-6 ( 63 ) Allergic Rhinitis (AR) Downregulated Nasal mucosa from AR patients and healthy volunteers Human Nasal Epithelial Cells (HNECs) ↑miR-193b → ↓ETS1 → ↓TLR4 → ↓ GM-CSF, eotaxin, MUC5AC Represses IL-13-induced inflammatory responses in nasal epithelial cells by suppressing ETS1/TLR4 signaling ( 6 ) Placenta Accreta Spectrum (PAS) Upregulated Human term placenta tissues (n = 8 for histological analysis/miRNA localization) JEG-3 (main functional model) BeWo (syncytialization model) Jurkat T cells (immune cell model for EV studies) HTR-8/SVneo (used as reference) Targets K-Ras, AKT1, TMPPE, SHMT2, PTK2, MCL1(validated) and NF1, ARPC5 (potential) Regulates key trophoblast functions by inhibiting migration, syncytialization, and apoptosis while promoting proliferation. Mediates immunosuppressive effects, reducing T-cell proliferation through extracellular vesicles ( 64 ) In-Stent Restenosis (ISR) Downregulated PBMCs from 63 subjects: ISR (n = 21), stent non-restenosis (n = 21), controls (n = 21) Not used (direct PBMCs analysis) Direct Target: PLAU (Plasminogen Activator, Urokinase) gene. Downregulation leads to elevated PLAU, promoting neointimal hyperplasia and ISR pathogenesis ( 65 ) Multiple Sclerosis (MS) Downregulated Blood samples from 30 MS patients (n = 30) and controls (n = 30) Not specified beyond luciferase assay Unknown Likely acts as a repressor of MS-related genes; Its downregulation/sponging by circ-cnot11-0001 is proposed to lead to the dysregulation of gene expression that contributes to MS pathogenesis ( 66 ) Myocardial Hypertrophy Not directly stated for miR-193b-5p Not specified Not specified LncRNA N29 → miR-193b-5p/TGFBR2 axis → Smad2/3 regulation Is mediated by lncRNA N29 to regulate the TGFBR2/smad2/3 axis and mitigate the progression of myocardial hypertrophy ( 67 ) Pulmonary Vascular Dysfunction associated with Diabetes/Metabolic Syndrome (HFpEF/EIPH/CpcPH context) Upregulated Primary human Pulmonary Artery Vascular Smooth Muscle Cells (PAVSMCs) from diabetic (n = 6) and non-diabetic controls (n = 6). Rat and human PAVSMCs Metabolic Stress → ↑ROS → H3K9 Acetylation of miR-193b Promoter → ↑ miR-193b → NFYA mRNA Degradation → ↓ NFYA → ↓ sGCβ1 Transcription→ ↓NO-sGC-cGMP Signaling → Impaired Pulmonary Arterial Vasodilation Links metabolic stress/ROS to pulmonary arterial dysfunction by degrading NFYA and shutting down the NFYA-sGCβ1-cGMP vasodilatory pathway ( 68 ) Endometriosis Downregulated in eutopic endometrium of women with endometriosis; upregulated in ectopic lesions (endometrioma) Cohort 1: 32 Women (endometriosis n = 15, controls n = 17) Cohort 2: 10 Women with endometrioma (paired ectopic & eutopic tissues collected) Human immortalized epithelial endometriotic cell (12Z), Endometrial stromal cell (HESC) ↑miR-193b → ↓ DKK1, MIEN1, GRB7, PIK3R1, KRT19 (direct/indirect targets) → ↓ activity of migration-related pathways (Wnt, PI3K–Akt, focal adhesion, cell adhesion) → Suppression of endometrial cell migration in vitro → May potentially limit spread of endometriotic lesions in vivo Suppresses endometrial cell migration; loss in eutopic tissue may promote implantation, while upregulation in ectopic lesions may limit spread ( 69 ) Hypertensive Disorder Complicating Pregnancy (HDCP) Upregulated (increases with disease severity) 120 HDCP patients vs. 120 healthy pregnant women and 120 non-pregnant controls Not investigated Works synergistically with Neurogulin-1 (NRG-1). NRG-1 may suppress Endocrine Gland-derived Vascular Endothelial Growth Factor (EG-VEGF) expression and block ERK signaling. Associated with onset, progression, and prognosis of HDCP; potential diagnostic and prognostic biomarker ( 70 ) Chronic kidney disease (CKD) following radical nephrectomy (RN) for renal cell carcinoma (RCC) Upregulated renal parenchyma (cortex & medulla) from 71 RCC patients post radical nephrectomy (FFPE) and renal biopsies (cortex) from healthy donors (n = 12) Not investigated Hypothesized to modulate TGF-β signaling (linked to TGF-β2 and TGFBR3). A predictive biomarker for post-operative CKD. Its overexpression is linked to renal inflammation and fibrosis, even in patients with no pre-operative signs of kidney disease ( 71 ) Alzheimer's Disease (AD) Upregulated in ABCA1-labeled exosomes Human serum: Controls (n = 60), SCD (n = 89), MCI (n = 92), DAT (n = 92); CSF; Controls (n = 6), MCI (n = 16), DAT (n = 11) Human RBCs, Human WBCs, Mouse hippocampal neuron HT-22 cells, Primary mouse neuronal cells Amyloid precursor protein (APP) Potential early diagnostic biomarker for AD ( 72 ) Summary of cell line/human studies on the role of miR-193b in non-malignant disorders. In many disorders, miR-193b levels are lower than normal. This loss of function often leads to dysregulated cell proliferation, inflammation, and tissue damage. For instance, in systemic sclerosis [ 53 ] and aortic dissection [ 54 ], miR-193b has a role in the regulation of the proliferation and migration of vascular smooth muscle cells, and modulation of vessel wall thickening and instability. Similarly, in “In-Stent Restenosis”, its downregulation leads to neointimal hyperplasia via the target gene PLAU [ 65 ]. It is also involved in the pathogenesis of inflammatory and autoimmune conditions. For instance, in psoriasis [ 60 ], allergic rhinitis [ 6 ] and sepsis [ 63 ], low levels of miR-193b result in hyperactivation of inflammatory pathways (like STAT3, NF-κB, and TCR signaling), driving keratinocyte proliferation, inflammatory secretion, and immune system overreaction. Its downregulation is also noted in endometriosis (in the original uterine tissue, potentially enabling cell migration) [ 69 ] and in some stages of Parkinson's disease [ 61 ], indicating a complex, stage-specific role in neurodegeneration. Conversely, in several other conditions, elevated miR-193b contributes to disease pathology. For instance, in type 2 diabetes [ 57 ] and prediabetes [ 59 ], increased miR-193b impairs glucose metabolism by enhancing hepatic glucose production and promoting insulin resistance. In a related finding, it also drives muscle atrophy (sarcopenia) in diabetic patients by disrupting protein synthesis [ 58 ]. Additionally, miR-193b contributes to the pathogenesis of neurodegenerative diseases. In Parkinson's disease (particularly late stage) [ 62 ] and Alzheimer's disease [ 72 ], upregulated miR-193b inhibits neuroprotective pathways (like PGC-1α), leading to mitochondrial dysfunction, oxidative stress, and neuronal damage. It is also investigated as a potential diagnostic biomarker in Alzheimer's disease [ 72 ]. In osteoarthritis, its increase with age promotes the degradation of the cartilage matrix [ 55 ]. In pulmonary vascular dysfunction linked to diabetes, it is upregulated by metabolic stress and disrupts a critical vasodilatory pathway [ 68 ]. It is also upregulated in placenta accreta spectrum [ 64 ] and hypertensive disorders of pregnancy [ 70 ], where it regulates trophoblast function and is associated with disease severity. From a mechanistical point of view, miR-193b frequently targets genes to control smooth muscle cell, keratinocyte, and trophoblast growth and movement. In addition, it can be regarded as a key regulator of major pro-inflammatory pathways, including NF-κB, STAT3 [ 60 ], and TCR signaling [ 63 ]. It is also involved in the glucose metabolism (via YWHAZ/FOXO1 and SOS2) [ 57 ], muscle protein balance (via Akt/mTOR) [ 58 ], and extracellular matrix remodeling (through regulation of MMPs [ 54 ] and ADAMTS5 [ 55 ]). Finally, as documented in the context of Parkinson's disease, it regulates mitochondrial function. In fact, its target PGC-1α is a master regulator of mitochondrial biogenesis and antioxidant responses [ 61 ]. In addition to the mentioned in vitro studies and expression assays in the clinical samples, the significant role of miR-193b in human disorders has been verified in animal models ( Table 3 ). The animal studies described in this table reveal miR-193b as a multifaceted molecule with significant roles in disease pathogenesis. Notably, it can function as a therapeutic target in aortic dissection [ 54 ], psoriasis [ 60 ], and diabetes-related muscle atrophy [ 58 ]. Moreover, miR-193 is a potential responsive biomarker for disease state and intervention efficacy in glucose intolerance [ 59 ]. In fact, miR-193 can be suggested as a key node in dysregulated signaling pathways across a spectrum of disorders, particularly in cardiovascular and metabolic diseases. Table 3 Summary of animal studies on the role of miR-193b in non-malignant disorders. Table 3 Type of disorder Animals Results References Aortic Dissection Apolipoprotein E-deficient (ApoE−/−) male mice (6–8 weeks old) Silencing H19 (with shH19) or directly increasing miR-193b-3p (with an agomir) in mice model: Reduced physical damage to the aorta (less degeneration, thinner aortic wall). Reversed the abnormal protein expression (increased α-SMA/SM22α; decreased MMP-2/MMP-9). ( 54 ) Influenza A Virus (IAV) Infection 8-week-old female 57BL/6J mice Adenovirus-mediated miR-193b delivery tended to reduce body-weight loss and significantly lowered lung viral load in H1N1-infected mice. ( 56 ) Psoriasis 7-week-old female C57BL/6 mice Overexpression of miR-193b-3p (agomiR-193b-3p) improved psoriasis symptoms, whereas inhibition (antagomiR-193b-3p) worsened them. ( 60 ) Myocardial Hypertrophy TAC-induced mice Silencing upstream lncRNA N29, which mediates the miR-193b-5p/TGFBR2 axis, improved cardiac function, reduced pathology, and inhibited hypertrophy. ( 14 ) Exercise-induced pulmonary hypertension (EIPH) in HFpEF ZSF-1 obese rats (HFpEF model) vs. Lean ZSF-1 rats (controls) EIPH phenotype: normal resting RVSP, markedly elevated during exercise. Molecular profile: ↑miR-193b, ↓NFYA, ↓sGCβ1, ↓cGMP. Functional impairment: blunted pulmonary arterial vasodilation without significant remodeling. ( 68 ) Combined pre- and post-capillary PH (CpcPH) in HFpEF ZSF-1 obese rats treated with SU5416 (CpcPH model) vs. Lean ZSF-1 rats (controls) CpcPH phenotype: elevated resting RVSP, severe exercise-induced worsening with RV hypertrophy Molecular profile: Same impaired pathway as EIPH model. Structural & functional impairment: Significant PA remodeling and vasodilation deficit. Therapeutic rescue: AAV6-NFYA gene therapy and SGLT2 inhibition both restored sGCβ1-cGMP signaling and improved exercise PH. ( 68 ) Glucose Intolerance 6-week-old male C57BL/6J mice Plasma miR-193b was significantly increased in glucose-intolerant HFD-fed mice compared to controls. The exercise intervention that improved glucose tolerance and reduced liver fat significantly decreased circulating miR-193b levels back towards baseline. Mirrored the human findings, validating its value as a responsive biomarker. ( 59 ) Diabetes and Prediabetes (in a gestational diabetes model) STZ-treated female mice and their offspring. miR-193b downregulated in diabetic mothers but upregulated in their offspring; proposed as a biomarker to differentiate diabetic and prediabetic states. ( 73 ) Alzheimer's Disease (AD) APP/PS1 double-transgenic mice (C57BL/6J background) vs. matched wild-type ABCA1-exosomal miR-193b increased in CSF and serum of APP/PS1 mice in an age-dependent manner; exosomes from AD mouse CSF trafficked to serum after injection. ( 20 ) Type 2 Diabetes (T2D) & Sarcopenia (Muscle Atrophy) C57BL/6J wild-type and db/db (T2D) mice miR-193b OE (C57): Induced muscle atrophy, dysfunction, and insulin resistance via PDK1/Akt inhibition. miR-193b KD (db/db): Rescued muscle loss, improved function and insulin sensitivity via PDK1/Akt activation. PDK1 KD (C57): Blocked miR-193b effects, confirming PDK1 as key target. ( 58 ) Summary of animal studies on the role of miR-193b in non-malignant disorders.

Sheyda Khalilian: Conceptualization, Data curation. Mohadeseh Fathi: Conceptualization, Data curation. Sara Arezi: Data curation. Soudeh Ghafouri-Fard: Supervision, Writing – original draft, Writing – review & editing.

Not applicable.

In the current narrative review, our objective was to identify and synthesize recent literature on the role of miR-193b (2019–2025) in any human disease, with a particular focus on cancer. We searched PubMed/MEDLINE and Google Scholar with the search string being structured in three core blocks: Block A: miR-193b; Block B: The Functional Role ((“Gene Expression Regulation” OR “Carcinogenesis” OR “Tumor Suppressor” OR “Oncogene” OR “OncomiR” OR “Pathogenesis” OR “Pathway” OR “Biomarker” OR “Diagnostic” OR “Prognostic” OR “Therapeutic” OR “Target” OR “Proliferation” OR “Apoptosis” OR “Migration” OR “Invasion” OR “Metastasis”); and Block C: Disease Context (Neoplasms OR Cancer OR Tumor OR Carcinoma OR Oncology OR Leukemia OR Lymphoma OR Non-malignant disorders). The final search combined these blocks as: A AND (B OR C). The search was restricted to English language. For article type, we initially had no restriction, but review articles were flagged for manual screening of their reference lists. All retrieved records were then exported into EndNote and duplicate records were removed. Subsequently, two independent reviewers screened titles and abstracts against pre-defined inclusion/exclusion criteria. Original research, case reports, or reviews that investigated miR-193b in the context of any human disease or biological process were included. Studies not involving humans or human-derived cell lines/tissues and studies not focused on miR-193b were excluded. Finally, data from included studies was extracted and tabulated capturing: Cancer/Disease Type, Expression Pattern, Samples/Cell Lines, Methods, Pathways/Interactions, Function, and References.

Not applicable.

No funding has been provided for the research.

Finally, we assessed miR-193b targets and related signaling pathways using in silico tools ( Table 4 , Table 5 ). The results strongly suggested that miR-193b is a key regulator of immune response, inflammation, and specific metabolic and signaling processes. Table 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of top miR-193b target genes. Table 4 Term P-value Genes Herpes simplex virus 1 infection 0.004482 ZNF33A; ZNF791; OAS2; CASP3; ZNF506; CCL5; ZNF627; ZNF107; ZNF780B; POU2F2; ZFP28; ZNF431 Cytokine-cytokine receptor interaction 0.00987 CCR1; BMP2; IL23R; CCL5; TNFSF10; TNFRSF11B; TNFRSF1B; CSF2RA Viral protein interaction with cytokine and cytokine receptor 0.018073 CCR1; CCL5; TNFSF10; TNFRSF1B Lipid and atherosclerosis 0.021298 CASP3; CCL5; TNFSF10; NFATC2; MAP2K7; POU2F2 TNF signaling pathway 0.026126 CASP3; CCL5; MAP2K7; TNFRSF1B Influenza A 0.029523 OAS2; CASP3; CCL5; TMPRSS4; TNFSF10 Salmonella infection 0.039495 VPS33A; CASP3; TNFSF10; MAP2K7; RAB7A; ARL8B Natural killer cell mediated cytotoxicity 0.042683 SHC4; CASP3; TNFSF10; NFATC2 Nicotinate and nicotinamide metabolism 0.047717 NMNAT1; SIRT2 Neomycin, kanamycin and gentamicin biosynthesis 0.049015 GCK Table 5 Gene ontology enrichment analysis of top miR-193b target genes using Enrichr online database ( https://maayanlab.cloud/Enrichr/ ). Table 5 GO Term Index Name P-value Adjusted p-value Odds Ratio Combined score Biological Process 1 Zinc Ion Import Across Plasma Membrane (GO:0071578) 0.002398 0.03458 571.06 3445.29 2 Protein Branched Polyubiquitination (GO:0141198) 0.005388 0.03458 235.02 1227.64 3 Intracellular Monoatomic Ion Homeostasis (GO:0006873) 0.005388 0.03458 235.02 1227.64 4 Regulation of Meiotic Cell Cycle (GO:0051445) 0.005986 0.03458 210.26 1076.21 5 Anaphase-Promoting Complex-Dependent Catabolic Process (GO:0031145) 0.006284 0.03458 199.74 1012.63 6 Zinc Ion Transmembrane Transport (GO:0071577) 0.006881 0.03458 181.56 904.00 7 Bile Acid and Bile Salt Transport (GO:0015721) 0.007477 0.03458 166.42 814.75 8 Zinc Ion Transport (GO:0006829) 0.007477 0.03458 166.42 814.75 9 Transition Metal Ion Transport (GO:0000041) 0.009265 0.03721 133.09 623.08 10 Negative Regulation of Epithelial to Mesenchymal Transition (GO:0010719) 0.01075 0.03721 114.05 516.95 Cellular Component 1 Anaphase-Promoting Complex (GO:0005680) 0.006284 0.03142 199.74 1012.63 Molecular Function 1 Bile Acid:Sodium Symporter Activity (GO:0008508) 0.001499 0.007788 999.50 6499.56 2 Interleukin-17 Receptor Activity (GO:0030368) 0.002098 0.007788 666.27 4108.59 3 Solute:Monoatomic Cation Symporter Activity (GO:0015294) 0.002997 0.007788 444.11 2580.41 4 Monoatomic Cation:Bicarbonate Symporter Activity (GO:0140410) 0.003595 0.007788 363.33 2044.88 5 Monocarboxylate:Sodium Symporter Activity (GO:0140161) 0.003894 0.007788 333.03 1847.77 6 Bile Acid Transmembrane Transporter Activity (GO:0015125) 0.005388 0.008974 235.02 1227.64 7 Bicarbonate Transmembrane Transporter Activity (GO:0015106) 0.006881 0.008974 181.56 904.00 8 Zinc Ion Transmembrane Transporter Activity (GO:0005385) 0.007179 0.008974 173.66 857.29 9 Transition Metal Ion Transmembrane Transporter Activity (GO:0046915) 0.01046 0.01162 117.41 535.47 10 Cytokine Receptor Activity (GO:0004896) 0.02465 0.02465 48.57 179.85 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of top miR-193b target genes. Gene ontology enrichment analysis of top miR-193b target genes using Enrichr online database ( https://maayanlab.cloud/Enrichr/ ). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the primary signaling and metabolic pathways that are significantly enriched with predicted miR-193b target genes. The most statistically significant pathways were dominated by viral infections and immune-inflammatory signaling. In details, multiple pathways related to viral pathogens were enriched, including Herpes simplex virus 1 infection, Influenza A, and viral protein interaction with cytokine receptors. Key targeted genes involved in these pathways included ‘CASP3’ (apoptosis), ‘CCL5’ (chemokine), ‘OAS2’ (antiviral response), and ‘TNFSF10’ (TRAIL, involved in immune cell killing). Among immune and inflammatory signaling pathways, “Cytokine-cytokine receptor interaction,” “TNF signaling pathway,” and “Natural killer cell mediated cytotoxicity” were prominently featured. This reinforces a central role for miR-193b in modulating the immune response. Finally, the “Lipid and atherosclerosis” pathway was significantly enriched, linking miR-193b to processes relevant to cardiovascular disease, which aligns with the animal study findings in aortic dissection and pulmonary hypertension. Gene Ontology analysis categorized the predicted functions of miR-193b target genes into three domains: Biological Process, Cellular Component, and Molecular Function. Among the Biological Process, involvement of miR-193b in processes like “Negative Regulation of T Cell Apoptosis,” “Positive Regulation of T-helper 17 Cell Differentiation,” and “Regulation of T Cell Activation” highlight a specific focus on adaptive immunity. Moreover, miR-193b is implicated in cell differentiation and growth factor signaling and extracellular matrix and transport pointing to potential roles of this miRNA in tissue structure and metabolite transport. “Cellular Component” analysis further indicated involvement of miR-193b in intracellular trafficking and signaling. Together, these computational predictions paint a coherent picture of miR-193b as a multifaceted regulator whose targets are heavily implicated in the regulation of immune and inflammatory responses, modulation of key signaling pathways, and control of cellular processes, such as apoptosis, maturation, and extracellular matrix dynamics. This predicted role in immune and inflammatory regulation provides a possible molecular explanation for its reported effects in animal models of disorders like psoriasis, viral infection, and cardiovascular disease. Finally, the predicted miR-193b targets were visualized using the Cytoscape software ( Fig. 1 ). Fig. 1 Correlation pairs of miR-193b targets, predicted by TargetScan online tool. The interaction network was constructed by Cytoscape software. Fig. 1 Correlation pairs of miR-193b targets, predicted by TargetScan online tool. The interaction network was constructed by Cytoscape software.

In the persistent search for novel diagnostic and therapeutic strategies, the field of molecular medicine has turned its focus to miRNAs. miR-193b exemplifies the promise of this class of molecules, functioning as both a critical “brake” on cellular growth and invasion and a promoter of tumorigenesis, based on the related context. Its frequent loss in some types of cancers such as gastric and cervical cancers as well as osteosarcoma positions it not only as a valuable prognostic indicator but also as a potential tool for gene therapy. On the other hand, it has been found to be up-regulated in esophageal and bladder cancers. Meanwhile, data regarding its expression pattern in some types of cancers, such as colorectal, lung and pancreatic cancers is conflicting. Mechanistically, miR-193b exerts its effects by targeting crucial genes and signaling pathways involved in oncogenesis. Differential expression of components of these pathways or ceRNA network interacting with this miRNA in different tissues or different stages of a certain type of cancer might explain the bidirectional or inconsistent expression and function of this miRNA. Notably, a previous meta-analysis of ten cohort studies has suggested miR-193b as an appropriate biomarker in the cancer prognosis for Asian patients [ 74 ], based on the association between down-regulation of miR-193b and poor overall survival rate in diverse human cancers. Furthermore, patients with lower levels of miR-193b have exhibited higher tendency to develop malignancies with higher potential of metastasis [ 74 ]. In some populations, to strengthen translational relevance, the diagnostic and prognostic performance of miR-193b across cancers has been reported. For example, in an Iranian cohort, miR-193b with the most area under the curve (AUC: 1.00, 95 % confidence interval 1.00–1.00, P < 0.0001) has exhibited a high discriminatory power for cutaneous melanoma [ 29 ]. Also, in another Iranian cohort the ROC curve analyses have confirmed the significance of miR-193b level as a potential biomarker for Parkinson's disease diagnosis (AUC: 0.7925, 95 % confidence interval: 0.6434–0.9416, P = 0.0016) [ 61 ]. Overall, across multiple diseases, dysregulated miR-193b expression associates with poor overall survival, supporting additive prognostic stratification alongside conventional clinicopathologic factors. Beyond oncology, the reach of miR-193b into conditions such as fibrosis and metabolic syndrome suggests a common mechanistic thread in human disease pathogenesis. The data from in vitro and in vivo studies suggests that miR-193b has significant clinical potential. It has a potential application as a diagnostic biomarker for prediabetes, Alzheimer's disease, and hypertensive disorders of pregnancy. Moreover, it can be a prognostic/predictive biomarker for assessment of the risk of developing chronic kidney disease after kidney cancer surgery and for the severity of hypertensive disorders of pregnancy. Finally, miR-193b has emerged as a promising therapeutic candidate because of its dysregulated activity across multiple diseases. Clinical translation requires careful monitoring of pharmacodynamics endpoints, including suppression of target proteins and circulating miRNA changes, alongside rigorous safety evaluation to address off-target effects. Scalable manufacturing of miRNA mimics and standardized preclinical toxicology are essential steps toward bringing miR-193b-based therapies into clinical practice, underscoring its potential as both a biomarker and a therapeutic agent. In conclusion, miR-193b is a powerful and versatile regulatory miRNA whose dysregulation is a common feature in the pathogenesis of numerous non-malignant diseases. Its pleiotropic nature makes it a compelling subject for further research, both for understanding disease mechanisms and for developing novel diagnostics and therapeutics. This timely update on the functional significance of miR-193b in human disorders and its role in disease-specific signaling networks paves the way for the translational progress towards clinical applications that could restore its protective function in patients.

The post-genomic era has uncovered the great significance of non-coding RNAs, with microRNAs (miRNAs) standing out as master regulators of post-transcriptional gene silencing. Dysregulation of these small RNA molecules is a hallmark of numerous pathological states, particularly cancer. Various studies have evaluated miRNA expression patterns and functions across different cancer types [ [1] , [2] , [3] ]. The great interest in this field is mainly due to the miRNA stability in circulating or other biofluids, and their potential as biomarkers for diagnostic and follow-up purposes. hsa-miR-193b (MI0003137) has been consistently identified as a key player in the carcinogenesis with both tumor-suppressive and oncogenic functions. This miRNA is encoded by MIR193B gene located in chr16:14,303,967–14,304,049 (GRCh38/hg38) Plus strand (Size: 83 bases). Its downregulation, mediated by promoter hypermethylation [ 4 ] or other mechanisms, leads to the unchecked expression of a number of oncogenes like CCND1 [ 5 ], ETS1 [ 6 ], and PLAU [ 7 ], thereby driving tumorigenesis, metastasis, and chemoresistance. Meanwhile, it exerts oncogenic roles in some types of cancer through down-regulating a number of tumor suppressors. Furthermore, emerging evidence positions miR-193b at the crossroads of other human diseases, including metabolic, inflammatory, and neurodegenerative disorders. This review provides a comprehensive overview of the latest research, synthesizing our current understanding of miR-193b′s multifaceted roles, its utility in clinical settings, and the challenges and opportunities in harnessing its power for future therapeutics. Additionally, the biological and molecular mechanisms of miR-193b functions as well as its regulatory mechanisms are discussed in the physiological and the pathological context. Finally, we highlight dysregulation of miR-193b in affected tissues and blood samples in several pathological conditions, particularly cancer.

Authors declare no conflict of interests.

The analyzed data sets generated during the study are available from the co-responding author on reasonable request.