{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA growing body of evidence indicates that miR‐873 (often referred to as miR‐873‑5p) plays context‐dependent roles in human disease, with a predominant tumor‑suppressive function in many cancers. In breast cancer, enforced expression of miR‑873 was shown to inhibit cell proliferation by targeting cell cycle regulators such as cyclin‑dependent kinase 3, while in glioblastoma and colorectal cancer its low expression correlated with aggressive phenotypes by failing to downregulate oncogenic targets like IGF2BP1 and TRAF5/TAB1 respectively. Likewise, in esophageal and cervical cancers, restoration of miR‑873 levels suppressed tumor cell growth, migration, and invasion by directly targeting genes including DEC2 and CXCL5/p53 modulators. In ovarian cancer, miR‑873 enhanced chemosensitivity by lowering MDR1 (ABCB1) expression, and in non‑small cell lung cancer (NSCLC) and bladder cancer, miR‑873 negatively regulated molecules involved in proliferation and metastatic signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to curbing tumor aggressiveness, miR‑873 modulates cellular responses to chemotherapeutic agents by influencing drug resistance pathways. In glioma cells resistant to cisplatin, overexpression of miR‑873 re‐sensitized cells through downregulation of the anti‑apoptotic Bcl‑2, whereas in ovarian cancer its upregulation reduced MDR1 expression and enhanced sensitivity to cisplatin and paclitaxel. Moreover, under high‑altitude hypoxic conditions, decreased miR‑873‑5p contributes to the elevation of drug transporter expression, suggesting that manipulation of miR‑873 may reverse chemoresistance in certain settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nA number of studies have also unveiled that miR‑873 operates within intricate competing endogenous RNA (ceRNA) networks. In several tumors, long non‑coding RNAs (lncRNAs) such as GAS5, DDX11‑AS1, TDRG1, and ERVK13‑1 have been reported to act as molecular “sponges” for miR‑873‑5p, thereby releasing its downstream targets from repression. In hepatocellular carcinoma, for instance, miR‑873 targeting of TRIM25 and PHF2 is attenuated by ceRNA interactions, which contributes to enhanced tumor cell migratory and invasive capacities. Similar ceRNA‑mediated regulatory mechanisms have been implicated in osteosarcoma and other settings, underscoring the complexity of miR‑873’s regulatory network."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond malignancies, miR‑873 influences diverse biological processes in non‑cancer settings. In systemic lupus erythematosus (SLE), increased miR‑873 expression in CD4⁺ T cells promotes their differentiation towards the pro‑inflammatory Th17 lineage by targeting the transcription factor Foxo1, thereby exacerbating disease severity. Furthermore, in congenital heart disease, elevated circulating miR‑873 inhibits cardiomyocyte proliferation via targeting GLI1, and in endothelial cells, modulation of miR‑873 by the lncRNA UCA1 impacts oxidative stress and inflammatory responses through the MAPK8 signaling pathway."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies in NSCLC, hepatocellular carcinoma, and papillary thyroid cancer further reinforce the multifaceted roles of miR‑873. Investigations in NSCLC indicate that miR‑873 regulates proliferation, invasion, and even chemoresistance—through modulation of the YWHAE/PI3K/AKT axis—while in HCC and thyroid cancer its dysregulation is linked with altered expression of key oncogenic proteins. Collectively, these findings highlight miR‑873 as a promising prognostic biomarker and potential therapeutic target across an array of human diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Cui, Y Yang, H Li, et al. 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