{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‐4516 has emerged as a critical regulator of tissue homeostasis and inflammatory responses. In mesenchymal stem/stromal cells from chronic kidney disease patients, melatonin‐induced upregulation of miR‐4516 enhances cellular prion protein expression and improves mitochondrial function, angiogenesis, and regenerative capacity. In psoriatic keratinocytes subjected to PUVA treatment, elevated hsa‐miR‐4516 directly suppresses STAT3 and its downstream survival factors, thereby promoting apoptosis. In addition, differential expression of miR‐4516 has been implicated in maintaining intercellular adhesion in airway epithelial cells during enterovirus infections, while its up‐regulation has also been documented in primary hypertension and in the urine of patients with premature ovarian insufficiency. Moreover, miR‐4516 modulates cell migration in neural crest–derived tissues, suggesting a role in the pathogenesis of Hirschsprung disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various neoplastic contexts miR‐4516 acts as a pivotal molecular switch—often functioning as a tumor suppressor—to modulate oncogenic signaling pathways. In breast cancer, reduced miR‐4516 levels in cancer‐associated fibroblast exosomes relieve suppression of FOSL1 and support triple‐negative breast cancer proliferation. Conversely, in glioblastoma multiforme overexpression of miR‐4516 enhances proliferation and invasive properties by directly targeting the tumor suppressor PTPN14 and modulating the Hippo pathway. In colorectal and pancreatic cancers, low levels of miR‐4516 contribute to increased expression of oncogenic targets such as OTX1, leading to enhanced cell proliferation, migration, and invasion. In gastric and hepatocellular carcinoma, competing endogenous RNA networks involving circular or long non‐coding RNAs sequester miR‐4516, thereby elevating STAT3/BclxL or SOX5 levels and promoting tumorigenesis. In lung adenocarcinoma, miR‐4516 upregulation impedes the Wnt signaling pathway through direct interaction with Wnt8B, resulting in cell cycle arrest and apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tissue regeneration and tumor biology, miR‐4516 also demonstrates potential as a biomarker in neuropsychiatric disorders. In cerebrospinal fluid extracellular vesicles isolated from suicide completers, altered levels of miR‐4516—along with other miRNAs targeting key regulatory molecules such as SLC6A4—highlight its promise as an indicator of pathological neural signaling and a potential target for future therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shruti Chowdhari, Neeru Saini "}, {"type": "b", "children": [{"type": "t", "text": "hsa-miR-4516 mediated downregulation of STAT3/CDK6/UBE2N plays a role in PUVA induced apoptosis in keratinocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.24608"}], "href": "https://doi.org/10.1002/jcp.24608"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24610393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24610393"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Shruti Chowdhari, Kabir Sardana, Neeru Saini "}, {"type": "b", "children": [{"type": "t", "text": "miR-4516, a microRNA downregulated in psoriasis inhibits keratinocyte motility by targeting fibronectin/integrin α9 signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Basis Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbadis.2017.08.014"}], "href": "https://doi.org/10.1016/j.bbadis.2017.08.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28844950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28844950"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yajie Hu, Jie Song, Longding Liu, et al. 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