{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐30b (miR‐30b), including its mature forms miR‐30b‐5p and miR‐30b‐3p, has emerged as a multifunctional regulator in diverse biological settings. In certain cancers its overexpression promotes malignancy—for example, in melanoma miR‐30b/30d upregulation enhances cellular invasion and immunosuppression by targeting GALNT7, thereby facilitating metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Conversely, in other tumor types such as colorectal cancer, miR‐30b acts as a tumor suppressor; forced expression induces G1 arrest and apoptosis by directly repressing oncogenes including KRAS, PIK3CD, and BCL2"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", while in esophageal and renal cancers it similarly inhibits proliferation, migration, and epithelial–mesenchymal transition via targets like HOXA1 and GNA13."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the context of reproductive biology, miR‐30b is upregulated in receptive endometrium where it is predicted to regulate genes involved in proliferation, apoptosis, and diverse signaling pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", whereas in acute myeloid leukemia lower levels of miR‐30b correlate with increased MYBL2 expression and poorer prognosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", highlighting its context‐dependent functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond tumor cell intrinsic roles, miR‐30b regulates key aspects of immune and stress responses. During microbial challenge, its upregulation in airway epithelial cells following respiratory syncytial virus infection suggests participation in the interferon response"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and ADAR1‐mediated RNA editing in target transcripts alters miR‐30b–dependent regulation of ARHGAP26."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " In models of phagocyte differentiation, overexpression of miR‐30b in monocytes and their derivatives attenuates phagocytosis and dampens pro‐inflammatory cytokine secretion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while proper downregulation during differentiation is necessary to mount full inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Moreover, in endothelial cells exposed to homocysteine, reduced miR‐30b levels correlate with enhanced caspase‐3 expression and apoptosis, with restoration of miR‐30b protecting against cell death."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In acute lung injury, decreased miR‐30b‐5p further contributes to elevated SOCS3 levels and exacerbated inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nmiR‐30b also exerts pivotal control over autophagy, angiogenesis, and metastasis. In gastric cancer, for instance, it suppresses metastasis by directly targeting SIX1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma its downregulation—whether due to sponging by lncRNAs that sequester miR‐30b‐5p or due to epigenetic promoter methylation—leads to enhanced autophagy via derepression of ATG5"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", thereby contributing to chemoresistance. In addition, miR‐30b overexpression in colorectal liver metastasis inhibits cell invasion through suppression of Rap1b"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and in osteoarthritis it targets ERG to modulate the expression of key cartilage matrix proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " In lung cancer, restoration of miR‐30b‐5p not only attenuates tumor growth and migration but also improves cisplatin sensitivity by targeting LRP8"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": ", while its circulating levels in plasma—and in exosomes in breast cancer and diabetic kidney disease—underscore its potential as a non‐invasive biomarker"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "24"}]}, {"type": "t", "text": " miR‐30b further regulates cellular metabolism, as exemplified by its role in hepatocellular lipid handling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ", and influences cell survival under endoplasmic reticulum stress by dampening the pro‐apoptotic eIF2α/ATF4/CHOP pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "26"}]}, {"type": "t", "text": " In prostate cancer, modulation of miR‐30b‐5p by circular RNAs affects radiosensitivity via targeting KIF18A"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "27"}]}, {"type": "t", "text": ", and a non‐canonical nuclear role has been revealed in which miR‐30b‐5p binds CLEAR elements to suppress TFEB‐dependent lysosomal biogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "28"}]}, {"type": "t", "text": " In osteosarcoma, miR‐30b is competitively inhibited by lncRNA MRPL23‐AS1, leading to derepression of MYH9 and activation of Wnt/β‐catenin signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": ", while in osteoarthritis its NF‐κB–induced upregulation mediates chondrocyte apoptosis through the SIRT1–FoxO3a–NLRP3 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": " Finally, in pancreatic ductal adenocarcinoma, hypoxic tumor cell–derived exosomal miR‐30b‐5p promotes angiogenesis by targeting GJA1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Avital Gaziel-Sovran, Miguel F Segura, Raffaella Di Micco, et al. 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