{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMicroRNA‐373 is emerging as a multifunctional regulator with unconventional activities in gene expression and as a circulating biomarker. In one pioneering study, miR‐373 was shown to bind complementary sequences within gene promoters—inducing, rather than repressing, the expression of targets such as E‐cadherin and CSDC2—demonstrating a non‐canonical mode of transcriptional activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, robust expression of miR‐373 (together with its cluster mates) has been detected in the serum of patients with germ‐cell tumours and aggressive forms of breast cancer, supporting its promise as a novel diagnostic marker; in these contexts, elevated exosomal miR‐373 correlates with triple‐negative breast carcinomas and other high‐risk clinical features."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer cells, however, miR‐373 exhibits context‐dependent oncogenic functions. In esophageal and hepatocellular carcinomas, for instance, miR‐373 directly targets key tumour suppressors such as LATS2 and PPP6C, thereby promoting cell cycle progression and proliferation. Similar oncogenic roles are evident in pancreatic cancer—where zinc‐mediated induction of miR‐373 represses TP53INP1, LATS2, and CD44—and in colorectal malignancies where upregulation of miR‐373 enhances stemness and drives epithelial–mesenchymal transition (EMT) by repressing differentiation‐promoting factors. In addition, in breast and other cancers, miR‐373 targets genes like TRPS1 and ITGA2 to foster cell migration and invasiveness, while in tongue squamous cell carcinoma its direct suppression of DKK1 contributes to Wnt/β‐catenin pathway activation and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast, miR‐373 can also manifest tumour‐suppressive and immunomodulatory effects depending on the cellular context. In ovarian and non‐small cell lung cancers, lower miR‐373 levels have been linked to enhanced tumour invasion, and its restoration suppresses migration by directly targeting Rab22a as well as IRAK2 and LAMP1. Furthermore, in viral infections such as those caused by HCV and HSV‐1, miR‐373 is up‐regulated and acts to dampen type I interferon signalling by targeting critical components (JAK1, IRF9, or IRF1), thereby favoring viral replication. In glioma, oncogenic long non‐coding RNAs sequester miR‐373–3p, suggesting that its normal function would counteract aberrant EGFR signalling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncology and infection, miR‐373 also modulates non‐cancerous pathologies and epigenetic processes. In osteoarthritis models, forced expression of miR‐373 protects chondrocytes from matrix degradation and apoptosis, mitigating cartilage destruction. Additionally, emerging data indicate a reciprocal modulation between miR‐373 and methyl‐CpG–binding proteins, underscoring its role in the intricate interplay between miRNAs and DNA methylation. Overall, as summarized in recent reviews, miR‐373’s diverse functions—including regulation of cell proliferation, EMT, immune evasion, and epigenetic control—highlight its potential both as a therapeutic target and as a biomarker in multiple diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robert F Place, Long-Cheng Li, Deepa Pookot, et al. 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