{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‐590, encompassing both its ‐5p and ‐3p strands, is emerging as a multifaceted regulator in diverse pathological conditions. In several studies, its dysregulated expression has been implicated in modulating cell proliferation, apoptosis, migration and invasion. For example, in some models of neurodegeneration and Alzheimer’s disease, altered miR‐590‐3p expression was correlated with changes in RNA‐binding proteins (e.g., hnRNP‐A1) (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma, miR‐590‐5p has been shown to control oncogenic signals by influencing the expression of factors such as Wnt5a, c‐Myc and cyclin D1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Studies in cervical cancer models revealed that miR‐590‐5p can act as an oncogene by post‐transcriptionally suppressing tumor suppressor CHL1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and in cardiovascular contexts, miR‐590 has been linked to the regulation of lipid metabolism via modulation of macrophage‐derived LPL."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the realm of cancer biology, miR‐590 functions in a context‐dependent manner. In colorectal cancer, for instance, an increase in miR‐590‐5p expression—induced by cell–cell contact or hypoxic conditions—has been associated with reduced YAP1 levels and inhibition of tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In glioblastoma and other highly aggressive tumors, miR‐590‐3p exerts tumor‐suppressive effects by targeting critical transcription factors such as ZEB1 and ZEB2, thereby inhibiting epithelial–mesenchymal transition (EMT)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Conversely, in endothelial cells exposed to oxidized LDL, miR‐590‐5p has been shown to interfere with apoptosis and downstream redox–MAPK–NF‐κB signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", while its roles in osteoblast differentiation and skeletal biology are mediated through targeting inhibitors like Smad7, ultimately stabilizing Runx2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In colorectal and other malignancies, manipulation of miR‐590‐5p affects angiogenesis and metastasis via the NF90/VEGFA axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", with additional studies in colon cancer and hypoxia highlighting its dualistic roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In osteosarcoma, enforced miR‐590‐3p expression suppresses proliferation and invasion by directly targeting oncogenic SOX9"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ", and in renal cell carcinoma, miR‐590‐5p functions as an oncomir by downregulating tumor‐suppressive PBRM1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional work in ovarian and gastric cancers has revealed that miR‐590‐3p can promote tumor development by targeting regulators such as FOXA2, cyclin G2 and FOXO3—modulating downstream factors like versican and β‐catenin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " In esophageal squamous cell carcinoma, loss of miR‐590‐3p activity, often due to its sequestration by oncogenic lncRNAs (for example, lncRNA‐ATB), has been linked to enhanced metastatic behavior mediated through upregulation of YAP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " In breast cancer, miR‐590‐3p overexpression contributes to apoptosis by targeting factors such as ATF3 and modulating Runx2 levels"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", whereas in gastric cancer, miR‐590‐5p directly targets FGF18 to attenuate tumorigenic signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Moreover, in models of chemoresistance and Hippo signaling—though less defined—the interplay of miR‐590 with key regulatory pathways has been suggested"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", and similar tumor‐suppressive roles of miR‐590‐3p have been observed in hepatocellular carcinoma through targeting critical transcriptional activators"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "as well as in breast cancer via modulation of SIRT1 and p53 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " Furthermore, in bladder cancer settings, regulatory networks involving miR‐590 appear to intersect with novel non-coding RNA molecules"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": ", and in ovarian cancer, miR‐590‐3p fosters an aggressive phenotype by directly repressing CCNG2 and FOXO3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncology, miR‐590’s impact has been extended to other vital physiological processes. In cardiac biology, miR‐590‐5p levels inversely correlate with differentiation cues in cardiosphere‐derived cells, suggesting an inhibitory role in cardiomyocyte maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": " In non‐small cell lung cancer, miR‐590‐5p exhibits tumor‐suppressive functions by targeting STAT3 and associated pro‐tumorigenic pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": ", and in cardiac fibroblasts its modulation of ZEB1 underlies anti‐fibrotic and anti‐migratory effects."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": " Moreover, in inflammatory conditions such as rheumatoid arthritis, aberrant sponging of miR‐590‐5p by lincRNAs leads to activation of MAPK signaling cascades"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": ", while in esophageal squamous cell carcinoma, lncRNA ESCCAL‐1 sequesters miR‐590‐3p to derepress APOBEC3G expression and promote malignant progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": " Finally, in non‐small cell lung cancer models, circular RNAs such as circPUM1 functionally sponge miR‐590‐5p to upregulate METTL3 and bolster tumor growth and glycolysis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chiara Villa, Chiara Fenoglio, Milena De Riz, et al. 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