{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‑382 is a versatile microRNA that has emerged as a critical regulator in diverse physiological and pathological processes. It fine‑tunes gene expression in a context‑dependent fashion, thereby influencing cell proliferation, differentiation, apoptosis, and migration across a wide spectrum of diseases—from cancer and fibrosis to neuropsychiatric disorders and beyond."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various malignancies, dysregulation of miR‑382 underlies distinct oncogenic or tumor‑suppressive programs. For instance, in osteosarcoma, reduced miR‑382 levels are associated with enhanced metastatic potential and chemoresistance"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", and in prolactinomas decreased miR‑382 correlates with resistance to dopamine agonists."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In ovarian and colorectal cancers, diminished miR‑382 expression promotes tumor progression by failing to restrain key targets—such as ROR1, NR2F2, and mediators involved in the KLF12/HIPK3 axis—as well as by engaging in a reciprocal relationship with oncogenic long non‑coding RNAs (e.g., NEAT1) that modulate ROCK1 activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": " Conversely, in a subset of breast cancers and in acute promyelocytic leukemia miR‑382 appears to function in an oncogenic manner by modulating targets such as RERG and PTEN"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "; its tumor‐suppressive role is also evident in prostate cancer and retinoblastoma, where restoration of miR‑382 inhibits proliferation and invasion through downregulation of COUP‑TFII and BDNF, respectively."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Moreover, miR‑382‑5p contained in cancer‑associated fibroblast‑derived exosomes has been shown to promote migration and invasion in oral squamous cell carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", and perturbation of ceRNA networks in colorectal cancer—such as those involving ZEB1—further underscores its pivotal role in modulating tumor cell behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumorigenesis, miR‑382 orchestrates multiple non‑neoplastic processes. During liver regeneration, it promotes hepatocyte proliferation via modulation of the PTEN–Akt axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": ", while in hematopoiesis its upregulation favors granulocyte commitment over megakaryocyte differentiation through targeting MXD1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Altered circulating levels of miR‑382 provide a promising noninvasive biomarker in ischemic stroke"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": ", and its dysregulation is implicated in HIV‑1 disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": " Furthermore, in skeletal muscle, silencing of miR‑382‑5p improves mitochondrial protein homeostasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": ", while its interaction with COL1A2 is linked to a reduced risk of osteoporotic fractures"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": "and its restoration in osteoarthritic chondrocytes attenuates inflammatory signaling via effects on CX43."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nmiR‑382 function is also finely tuned by networks of competing endogenous RNAs and long non‑coding RNAs, which in turn modulate chemoresistance and metastatic behavior. For example, in the tumor microenvironment, circular RNAs such as circ_0001178 sequester miR‑382‑5p to regulate oncogenic VEGFA expression in hepatocellular carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": "and in colorectal cancer via a PTEN‑dependent mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Similarly, in pancreatic cancer, miR‑382 targets annexin A3 to suppress epithelial–mesenchymal transition"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": ", and in glioma forced overexpression of miR‑382 attenuates malignant behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": " Furthermore, in cervical cancer the LINC00707/miR‑382‑5p/VEGFA axis plays a key role in metastasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", in lung squamous cell carcinoma an H3K4me1‑induced lncRNA (DLX6‑AS1) modulates secondary cisplatin resistance via the miR‑382‑5p/CELF1 axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", and in chronic thromboembolic pulmonary hypertension upstream regulatory mechanisms affect miR‑382‑3p expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": " In infantile pneumonia, the LINC00707/miR‑382‑5p/NKAP regulatory loop further implicates miR‑382 in controlling inflammatory responses"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "32"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma and breast cancer the modulation of miR‑382–regulated pathways influences invasive properties and macrophage polarization, respectively."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "33"}]}, {"type": "t", "text": " Finally, miR‑382 also contributes to the invasive behavior of oral squamous cell carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "and has been implicated in the regulation of gene networks in infantile hemangiomas."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alison J Kriegel, Yi Fang, Yong Liu, et al. 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