{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMiR‐95 is frequently dysregulated in human cancers and often exerts oncogenic functions by promoting tumor growth, metastasis, and resistance to both chemotherapy and radiotherapy. For example, in prostate cancer forced expression of miR‐95 enhances radiation resistance and aggressive cellular phenotypes via downregulation of key regulators such as SGPP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Elevated miR‐95 levels have also been reported in non–small cell lung cancer (NSCLC) where overexpression contributes to tumor growth and radioresistance, including in stem‐like ALDH1(+)CD133(+) subpopulations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In lung adenocarcinoma with brain metastasis, miR‐95–3p suppresses cyclin D1 expression, thereby inhibiting invasiveness and clonogenicity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in gliomas miR‐95–3p directly targets CELF2 to promote proliferation and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while in hepatocellular carcinoma its upregulation reduces p21/CDKN1A expression, accelerating cell cycle progression and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In thyroid nodular disease, circulating miR‐95–3p—in combination with other miRNAs—has been suggested as a diagnostic marker of malignancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, exosomal delivery of miR‐95 by tumor‐associated macrophages promotes epithelial–mesenchymal transition in prostate cancer by targeting JunB"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and emerging studies in colorectal and colon cancers implicate miR‐95 in modulating tumor behavior through regulatory axes—including targets such as FOXD1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "—as well as in gastric cancer, where its overexpression in the intestinal subtype contributes to chemoresistance via an EMP1/PI3K–Akt axis, while differential expression is observed in signet ring cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Finally, in cholangiocarcinoma, miR‐95–3p acts as an oncogenic factor by downregulating TRAF3 to stimulate cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNotably, the functional outcome of miR‐95 dysregulation appears highly context‐dependent. In osteosarcoma, contrasting evidence exists: one study associates elevated serum miR‐95–3p levels with advanced clinical stage and enhanced tumor cell growth via modulation of the TGF‐β/p21/cyclin D1 axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", whereas another demonstrates that enforced miR‐95–3p expression suppresses tumor growth by targeting hepatoma‐derived growth factor (HDGF) and promoting apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " In addition, miR‐95 targeting of SCNN1A in osteosarcoma cells further supports a role in promoting cell cycle progression and survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Ongoing investigations in prostate cancer are also beginning to define the multifaceted activities of miR‐95, although its precise role in this context remains to be fully elucidated."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncogenesis, miR‐95 plays roles in nonmalignant conditions and holds promise as a diagnostic biomarker. In osteoarthritis, chondrocyte‐derived exosomes enriched in miR‐95–5p promote cartilage development and matrix synthesis by directly targeting HDAC2/8, suggesting a potential disease‐modifying application."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Furthermore, in multiple sulfatase deficiency, miR‐95 negatively regulates SUMF1 expression, leading to reduced sulfatase activity and impaired proteoglycan catabolism—a finding that highlights its regulatory capacity in metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": " Collectively, these studies illustrate the multifaceted roles of miR‐95 in both pathological and physiological contexts, emphasizing its potential as a therapeutic target and biomarker across a spectrum of human diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}, {"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xiaoyong Huang, Samira Taeb, Sahar Jahangiri, et al. 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