{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐761 (miR-761) is emerging as a multifaceted regulator whose function is highly context-dependent across various malignancies. In several cancers, diminished miR-761 levels or its sequestration by competing endogenous RNAs has been linked to tumor progression. For example, in ovarian cancer, miR-761 is downregulated, and its restoration limits cell proliferation and invasion by directly targeting oncogenic mediators such as MSI1 and LETM1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In colorectal cancer, decreased miR-761 expression is associated with enhanced tumor growth, with reintroduction of miR-761 suppressing proliferation and invasion via direct inhibition of both HDAC1 and MAPK1; these effects are further modulated by the sponging action of lncRNA PVT1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In osteosarcoma, miR-761 acts as a tumor suppressor by targeting IRS1, an effect counterbalanced by its sequestration by ADIRF-AS1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In glioma, one study demonstrated that sponging of miR-761 by hsa_circ_0007534 releases ZIC5 from repression, thereby promoting cell proliferation and migration"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", whereas another study in temozolomide-resistant glioma showed that overexpression of miR-761—by targeting PIM1—enhances chemosensitivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In hepatocellular carcinoma, conversely, miR-761 is upregulated and exerts oncogenic effects by targeting Mitofusin-2 to impair apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Further highlighting its dualistic nature, investigations in non-small cell lung cancer revealed that miR-761, whose function is modulated by binding to lncRNA FENDRR, downregulates TIMP2 and thereby facilitates tumor aggressiveness"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", while studies in triple-negative breast cancer and synovial sarcoma implicate miR-761 in the modulation of chemoresistance and cell viability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in neoplasia, miR-761 contributes to the regulation of stress responses and homeostasis in non-cancerous conditions. In atherosclerosis, miR-761 exhibits an atheroprotective role by modulating the mTOR–ULK1 signaling pathway to promote autophagy in macrophage-derived foam cells, thereby reducing inflammatory cytokine production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In cardiomyocytes exposed to hypoxia—as seen in acute myocardial infarction—miR-761 confers protection by targeting MAP3K2, which lessens inflammation, apoptosis, and oxidative stress."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In the context of diabetic retinopathy, reduced miR-761 activity, mediated by its sequestration via circSLC16A10, results in enhanced MFN2 expression and consequent improvements in mitochondrial function and cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Similarly, in osteoarthritis, miR-761 fine-tunes autophagy in chondrocytes by regulating FBXO21 levels, further emphasizing its role in controlling inflammatory and degenerative processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Can Shi, Zhenyu Zhang "}, {"type": "b", "children": [{"type": "t", "text": "miR-761 inhibits tumor progression by targeting MSI1 in ovarian carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13277-015-4377-z"}], "href": "https://doi.org/10.1007/s13277-015-4377-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26563371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26563371"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lieting Ma, Wenyan Liu, Miaoling Li "}, {"type": "b", "children": [{"type": "t", "text": "Circ_0061140 Contributes to Ovarian Cancer Progression by Targeting miR-761/LETM1 Signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Genet (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10528-022-10277-6"}], "href": "https://doi.org/10.1007/s10528-022-10277-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36056285"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36056285"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wei Xiong, Shu Yang, Wanfu Zhang, et al. 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