{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐876 (miR-876), including its −5p and −3p isoforms, emerges as a versatile regulatory molecule whose altered expression contributes to a wide array of human diseases. In various cancers and non‐malignant disorders, miR-876 has been shown to balance cellular proliferation, differentiation, apoptosis and even antiviral host responses by repressing the translation of specific target mRNAs. This microRNA is intricately regulated by, or itself regulates, several noncoding RNAs (for example, circular RNAs and long noncoding RNAs that serve as sponges) thereby modulating key oncogenic and inflammatory pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the cancer context, miR-876 frequently functions as a tumor suppressor. In esophageal squamous cell carcinoma, for instance, the circular RNA ciRS-7 sponges miR-876-5p, thereby diminishing its tumor-repressive effects on downstream MAGE-A family targets, which promotes proliferation, migration and invasion. In hepatocellular carcinoma, miR-876-5p has been documented to inhibit metastasis by targeting BCORL1 and DNMT3A, while in lung cancer it suppresses epithelial-to-mesenchymal transition by directly downregulating BMP-4. Similar tumor-suppressive mechanisms have been reported in gastric cancer (via targeting WNT5A and MITF), colorectal cancer (targeting RASAL2), osteosarcoma (through c-Met), and cervical cancer (via c-Met modulation). Additionally, long noncoding RNAs such as PITPNA-AS1 and LINC01315, as well as circular RNAs like circTP53 and circ_0016760, contribute to tumor progression by sponging miR-876-5p or miR-876-3p, leading to the upregulation of oncogenes such as WNT5A, GRK5, CDKL3, NOVA2, and others in triple-negative breast cancer, non-small cell lung cancer, and endometrial cancer. Finally, recent studies also extend the tumor suppressive role of miR-876 to melanomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncology, the miR-876 family plays pivotal roles in non-cancerous conditions. In severe enterovirus 71 (and EV-A71) infections, elevated miR-876-5p levels serve as a specific cellular response that, when experimentally reduced, correlate with decreased viral RNA replication and milder disease severity. In neonatal lung disease, particularly bronchopulmonary dysplasia, diminished miR-876-3p is linked to impaired alveolar development, whereas its functional restoration improves lung architecture. Moreover, in psoriasis, miR-876-5p downregulation contributes to keratinocyte hyperproliferation and aberrant signaling via modulation of Angiopoietin-1 and downstream pathways. Finally, in metabolic settings, miR-876-3p regulates adiponectin expression in adipocytes, thereby influencing insulin signaling and resistance, and its altered expression has emerged as a potential diagnostic biomarker in colon cancer and a contributor to tamoxifen resistance in breast cancer via regulation of ACTN4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert Y L Wang, Kuo-Feng Weng, Yhu-Chering Huang, et al. 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