{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐18b has emerged as a critical regulatory microRNA in diverse cancer types. In breast cancer, for example, miR‐18b (often co‐expressed with miR‐18a) directly targets estrogen receptor‐α, thus contributing to the ER‐negative and basal‐like phenotypes, while aberrant promoter methylation of its gene has been observed in sporadic tumors. In melanoma, miR‐18b modulates the MDM2–p53 pathway, and in nasopharyngeal carcinoma, loss of CTGF causes an upregulation of miR‐18b that in turn promotes cell proliferation. In mantle cell lymphoma, elevated miR‐18b levels are associated with poor prognosis and may, by decelerating cell proliferation, contribute to chemoresistance. Moreover, elevated miR‐18b expression has been reported in a subset of breast tumors that display enhanced migratory capacity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMiR‐18b is also implicated in regulating chemoresistance and differentiation programs through interactions with various noncoding RNAs. In colorectal cancer, circular RNAs such as circ‐FBXW7 and circ‐FBXW4 bind miR‐18b–5p (or its isoform miR‐18b–3p) to modulate oxaliplatin sensitivity and reduce chemoresistance. In lung adenocarcinoma and in oral squamous cell carcinoma, long noncoding RNAs (e.g., ZFPM2‐AS1 and circ‐CLK1) act as sponges for miR‐18b–5p, thereby influencing cell proliferation, epithelial–mesenchymal transition, and invasion. In addition, miR‐18b participates in differentiation processes; its downregulation in hair follicle mesenchymal stem cells lifts suppression of SMAD2, promoting smooth muscle differentiation, while in embryonal carcinoma cells, miR‐18b targets FOXN1 to steer epithelial lineage development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its cancer‐related roles, miR‐18b is involved in several pathological contexts where metabolic and proliferative processes are dysregulated. In diabetic retinopathy and nephropathy, altered miR‐18b levels impact cell proliferation, VEGF secretion, and extracellular matrix deposition by modulating targets such as the IGF‐1/IGF1R axis and HMGA2. In hepatitis C–associated hepatocellular carcinoma, increased serum miR‐18b levels show promise as a non‐invasive biomarker. In esophageal squamous cell carcinoma, miR‐18b–5p targets FBP1 to link fatty acid metabolism with tumorigenesis, while in polycystic ovary syndrome, exosome‐derived miR‐18b–5p modulates PTEN and the PI3K/Akt/mTOR signaling cascade. In osteosarcoma, hypoxia‐induced miR‐18b–5p upregulation (mediated by HIF‐1α) promotes proliferation and metastasis via suppression of the tumor suppressor PHF2. Furthermore, in preeclampsia, extracellular vesicle–derived miR‐18b downregulates Notch2 to enhance trophoblast proliferation and migration, and in breast cancer, a long noncoding RNA (LINC00467) has been shown to act as a competing endogenous RNA for miR‐18a/b–5p, leading to MAPK4 upregulation and increased cell growth. Computational analyses additionally suggest that miR‐18b contributes to sex‐biased gene expression profiles that may influence immune cell abundances."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S-K Leivonen, R Mäkelä, P Ostling, et al. 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