{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that miR‐1225‐5p plays multifaceted roles in cancer biology. In gastric carcinoma, for example, profiling of exosomal miRNAs in peritoneal fluids identified miR‐1225‐5p as highly expressed in malignant ascites and in lavage samples, suggesting its potential as a biomarker for peritoneal dissemination."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Complementing these findings, functional investigations demonstrated that, in gastric cancer tissues, miR‐1225‐5p is frequently downregulated and its ectopic overexpression suppresses tumor cell proliferation, migration, and invasion—mediated at least in part via inhibition of insulin receptor substrate 1 and subsequent dampening of β‐catenin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn other tumor types, the role of miR‐1225‐5p appears to be context dependent. In laryngeal carcinoma, lower expression of this miRNA is linked with increased cell survival and proliferation, whereas its overexpression induces G1/S cell cycle arrest and cell death by directly targeting CDC14B."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in thyroid cancer, miR‐1225‐5p levels are diminished relative to normal tissues; increasing its expression inhibits proliferation, migration, and invasion through direct targeting of SIRT3 and subsequent suppression of the Wnt/β‐catenin pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In osteosarcoma, miR‐1225‐5p acts as a tumor suppressor by directly repressing Sox9, thereby curtailing malignant phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Conversely, studies in pancreatic and breast cancers indicate that miR‐1225‐5p may be upregulated, where its elevated levels correlate with disease progression; in these contexts, targeting of Janus kinase 1 (JAK1) appears to be a critical mechanism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In ovarian cancer, exosomal miR‐1225‐5p derived from hypoxic tumor cells supports malignant progression by promoting M2‐like macrophage polarization via downregulation of Toll‐like receptor 2 and activation of the Wnt/β‐catenin pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its involvement in tumorigenesis, miR‐1225‐5p also plays regulatory roles in non‐malignant processes. In adult renal progenitor cells, for instance, reduced miR‐1225‐5p levels are associated with heightened expression of key progenitor markers such as PAX2 and CD133, as well as with elevated levels of TLR2, thereby influencing stemness and repair capabilities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Additionally, preliminary investigations in hepatocellular carcinoma suggest that miR‐1225‐5p may have an important, yet not fully elucidated, impact on tumor cell growth, migration, and invasion, warranting further study to clarify its precise role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Motohiko Tokuhisa, Yasushi Ichikawa, Nobuyoshi Kosaka, et al. 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