{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nmiR‐766 has emerged as an important regulator of diverse physiological processes. In aging human cells, miR‐766 post‐transcriptionally downregulates SIRT6, thereby influencing genome stability, telomere integrity, DNA repair, and the efficiency of cellular reprogramming, suggesting a feedback loop between SIRT6 and miR‐766 in aging fibroblasts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, miR‐766 has been implicated in endocrine regulation where it displays allele‐selective binding to the 3′UTR of the aldosterone synthase gene, potentially moderating its expression and impacting blood pressure homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cancer arena, miR‐766 exhibits context‐dependent and often dichotomous roles. In glioma, for instance, circular RNA (circATP8B4) carried in extracellular vesicles functions as a sponge for miR‐766‐3p, thereby promoting radioresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In renal cell carcinoma, hypermethylation of the miR‐766‐3p promoter correlates with its downregulation, and re‐expression attenuates cell‐cycle progression by targeting SF2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Hepatocellular carcinoma (HCC) studies have revealed apparently conflicting roles: one report shows that miR‐766 promotes cell proliferation and metastasis by repressing NR3C2 and modulating β‐catenin signaling"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", whereas another study demonstrates that upregulation of miR‐766‐3p reduces HCC aggressiveness by directly targeting Wnt3a and dampening downstream oncogenic signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In colon cancer cells, miR‐766 targets DNMT3B, leading to reduced methylation of key tumor suppressor genes and diminished proliferation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", while in esophageal squamous cell carcinoma, elevated serum exosomal miR‐766‐3p enhances cell migration and invasion through its direct regulation of HOXA13, correlating with poor patient outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, in breast cancer, miR‐766 augments wild‐type p53 signaling by directly inhibiting its negative regulator MDM4"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and additional studies have shown that miR‐766‐5p can suppress oncogenic pathways by targeting CBP and BRD4, thereby downregulating MYC."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Further complexity is added by evidence in colon cancer where miR‐766‐5p targets pro‐apoptotic genes (BAX, BAK, and BOK) to temper mitochondrial apoptosis and promote cell viability"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and in HCC, wherein circ_0021093 acts as a competing endogenous RNA to sequester miR‐766‐3p, leading to enhanced expression of metastasis‐associated MTA3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In laryngeal squamous cell carcinoma, miR‐766‐5p normally targets HMGA2 to impede tumorigenesis; sponging of miR‐766 by circSHKBP1 relieves this suppression and accelerates malignant progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Reports have also documented aberrant miR‐766 expression in colon"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "and cervical cancers"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", further underscoring its multifaceted function in oncogenesis.\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in tumor biology, miR‐766‐3p contributes to the modulation of inflammatory and injury responses. In rheumatoid arthritis, one study demonstrated that circ_0088194 sequesters miR‐766‐3p, thereby relieving repression on MMP2 and facilitating fibroblast‐like synoviocyte invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ", while another report identifies miR‐766‐3p as an anti‐inflammatory factor that diminishes NF‐κB activation and inflammatory gene expression in synoviocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " In cerebral ischemia/reperfusion injury, a lncRNA/miR‐766‐3p/NR3C2 axis has been implicated in regulating neuronal survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Finally, in models of aristolochic acid‐induced hepatotoxicity, miR‐766‐3p attenuates the induction of NQO1, thereby alleviating oxidative stress and cellular damage"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": ", and further, circ_0000479 modulation of miR‐766 activity influences FKBP5 expression in rheumatoid arthritis, underscoring its broader significance in inflammatory disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Amit Sharma, Sebastian Diecke, Wendy Y Zhang, et al. 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