{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that miR‐425 (including both its –3p and –5p isoforms) plays multifaceted roles in tumorigenesis. In several cancers, including breast, gastric, colorectal, esophageal, cervical, prostate, hepatocellular, renal, osteosarcoma, glioblastoma, and ovarian carcinomas, miR‐425 can act either as an oncogene or as a tumor‐suppressive factor depending on cellular context. For instance, the miR‐191/425 cluster is estrogen‐responsive in breast cancer and contributes to the regulation of proliferation, apoptosis, and metastasis by targeting key tumor suppressors such as PTEN, FOXD3, PDCD10, and SMAD2; similarly, in colorectal, gastric, and esophageal cancers, aberrant miR‐425 expression is linked to chemoresistance and enhanced malignant behavior through modulation of downstream effectors. Moreover, studies in prostate cancer and hepatocellular carcinoma have demonstrated that miR‐425 upregulation correlates with poor prognosis and chemoresistance, while its dysregulation in clear cell renal carcinoma, laryngeal carcinoma, and KRAS‐mutated colorectal cancer further underscores its pivotal function in dictating tumor aggressiveness and therapeutic response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "24"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer, miR‐425 also exerts significant effects in cardiovascular and neurological settings. Notably, in the heart, miR‐425 regulates the production of atrial natriuretic peptide by binding to NPPA mRNA in an allele‐specific manner, thereby influencing blood pressure and responses to salt overload. In the central nervous system, miR‐425 deficiency has been implicated in promoting necroptosis of dopaminergic neurons—a process linked to the pathogenesis of Parkinson’s disease—and has also been associated with differential expression in the context of antidepressant treatment response, suggesting neuromodulatory as well as vascular roles mediated via NF‑κB–dependent pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, miR‐425 is emerging as an important modulator of immune responses and aging. Elevated miR‐425 expression in T helper 17 cells has been shown to promote pathogenic differentiation in inflammatory bowel disease through targeting Foxo1, whereas reduced levels of miR‐425 in centenarians and patients with rheumatoid arthritis suggest a possible role in mediating immune homeostasis and longevity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Gianpiero Di Leva, Claudia Piovan, Pierluigi Gasparini, et al. 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