{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐188 (miR‐188), including its mature forms miR‐188‐3p and miR‐188‐5p, is a multifunctional regulator of normal physiology. It modulates the fate of bone marrow mesenchymal stem cells—promoting an age‐dependent shift from osteogenesis to adipogenesis and thereby contributing to bone loss"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " miR‐188 is also implicated in immune regulation; its aberrant upregulation in T cells is associated with altered DNA methylation of X‐linked immune genes and may predispose to lupus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, miR‐188 expression is sensitive to cellular stress such as UV irradiation and hypoxia—suggesting a role in cell cycle control"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "—and it participates in spermatogenesis via modulation of MLH1 levels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in healthy tissues, miR‐188 contributes to non‐malignant pathologies. In hepatic fibrosis models, elevated miR‐188‐5p enhances hepatic stellate cell activation and fibrogenesis by targeting PTEN and stimulating the AKT pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In benign fibrotic conditions such as keloids and hypertrophic scars, increased miR‐188‐5p expression suppresses cellular proliferation, migration, and invasion via inhibition of PI3K/AKT and MMP‐mediated signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In rheumatoid arthritis, downregulation of miR‐188‐5p in synovial fibroblasts correlates with enhanced cell motility and extracellular matrix remodeling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while in stroke models, overexpression of miR‐188‐5p modulates neuronal apoptosis through regulation of PTEN."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Altered miR‐188‐3p expression is also observed in polycystic ovary syndrome, suggesting its involvement in ovarian dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cancer arena, miR‐188 plays complex, context‐dependent roles that can be either tumor suppressive or oncogenic. In prostate cancer, for example, downregulation of miR‐188‐5p is linked to enhanced proliferation and metastasis through effects on targets such as LAPTM4B"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", while in colorectal cancer, high miR‐188‐3p expression serves as an independent prognostic indicator and promotes migration by directly interacting with MLLT4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In acute myeloid leukemia, competing endogenous RNAs such as SBF2‐AS1 sequester miR‐188‐5p to regulate ZFP91 expression and affect patient outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In gastric cancer, miR‐188‐5p has been reported with seemingly divergent roles: it can act as a tumor suppressor by targeting ZFP91"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "yet also promote proliferation via upregulation of SALL4 and subsequent suppression of PTEN."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " In breast cancer, intracellular re‐expression of miR‐188‐5p inhibits proliferation and migration by downregulating Rap2c"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", whereas differential serum and exosomal levels of miR‐188‐5p offer potential diagnostic value."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " In oral squamous cell carcinoma, miR‐188‐5p suppresses tumor progression by targeting SIX1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "and is itself regulated by competing endogenous RNAs such as the MMP1 3′UTR"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "and circRNAs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In glioma, restoration of miR‐188 reduces β‐catenin levels to impede cell cycle progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma, lncRNA CASC11 suppresses miR‐188‐5p to favor tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": " In lung adenocarcinoma, lncRNA DARS‐AS1 impairs miR‐188‐5p function, thereby promoting proliferation, invasion, and activation of the PI3K/AKT pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Other malignancies reflect similar complexity: in bladder cancer, concomitant high expression of miR‐188‐5p and miR‐141‐3p correlates with aggressive tumor behavior"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "; in multiple myeloma, overexpression of miR‐188‐5p inhibits cell viability and tumor growth"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": "; in osteosarcoma, miR‐188‐5p impairs progression by degrading CCNT2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": "and by targeting SOX4"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "; and in hepatocellular carcinoma, lncRNA PAPAS downregulates miR‐188‐5p to influence tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": " Additional regulatory layers are provided by ceRNA networks—for instance, lncRNA SNHG15 modulates miR‐188‐5p activity in oral cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": "and, in papillary thyroid carcinoma, miR‐188‐5p suppresses proliferation via targeting FGF5."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": " Moreover, in hepatocellular carcinoma, circ_0016142 sequesters miR‐188‐5p to induce ferroptosis through GPX4"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": ", while in glioblastoma, miR‐188‐3p exerts oncogenic effects by targeting GPR26."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": " In gallbladder carcinoma, reduced miR‐188‐5p expression is associated with larger tumor size and metastasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": ", and in breast cancer, restoration of miR‐188‐5p suppresses tumorigenesis by downregulating ZFP91/NF‐κB signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "34"}]}, {"type": "t", "text": " Further modulation of miR‐188 is observed in cervical cancer through lncRNA DARS‐AS1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "35"}]}, {"type": "t", "text": "and in cervical squamous cell carcinoma via circRNA networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "36"}]}, {"type": "t", "text": " Finally, preliminary studies in lung adenocarcinoma and ovarian cancer suggest that modulation of miR‐188 affects cellular proliferation and apoptosis through mechanisms that remain to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chang-Jun Li, Peng Cheng, Meng-Ke Liang, et al. 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