{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‐345 has emerged as a tumor‐suppressive microRNA in several malignancies. In colorectal cancer, its expression is frequently silenced by promoter hypermethylation, and restoration of miR‐345 inhibits cell proliferation and invasiveness by targeting anti‐apoptotic molecules such as BAG3, thereby correlating with less aggressive disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In pancreatic cancer, miR‐345 is one of the most significantly downregulated miRNAs, suggesting a potential tumor‐suppressive role awaiting further exploration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In non‐small cell lung cancer, decreased levels of miR‐345 are linked to gefitinib resistance, and re‐establishing its expression induces cell cycle arrest through suppression of MAPK1 and modulation of MAPK/c‐Fos and AKT/Bcl‐2 signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, in hepatocellular carcinoma, reduced miR‐345 expression is associated with poorer clinical features, and its forced expression inhibits migration and invasion by directly targeting YAP1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In gastric cancer, low miR‐345 levels correlate with lymph node metastasis and advanced stage; functionally, its enforced expression suppresses migration, invasion, and epithelial–mesenchymal transition by targeting factors such as FOXQ1 and EPS8 to modulate Rac1 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In breast cancer, a long non‐coding RNA (RACGAP1P) acts as a competing endogenous RNA for miR‐345‐5p, thereby relieving repression of its parental oncogene RACGAP1, which promotes mitochondrial fission and enhances metastatic potential."}, {"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 oncological functions, miR‐345 also displays potential as a prognostic and predictive biomarker. In locally advanced rectal cancer, elevated circulating miR‐345 levels are significantly associated with resistance to preoperative chemoradiotherapy and poorer local recurrence‐free survival, suggesting its utility for patient stratification in personalized treatment approaches."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, in multiple sclerosis, altered expression of miR‐345‐5p alongside other differentially expressed miRNAs in blood samples points to its promise as a minimally invasive biomarker reflective of underlying immunological and neurological dysregulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to these roles, miR‐345 exerts antifibrotic effects in hepatic pathology. In activated hepatic stellate cells and fibrotic livers, miR‐345‐5p is markedly downregulated; its overexpression suppresses the production of profibrotic markers and cell proliferation by directly targeting hypoxia‐inducible factor 1α (HIF‐1α) and consequently modulating the TGF‐β/Smad signaling cascade, thereby ameliorating liver fibrosis in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jie-Ting Tang, Ji-Lin Wang, Wan Du, et al. 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