{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMIR9‐2HG, also known as LINC00461, is emerging as a multifunctional long noncoding RNA with oncogenic properties across various cancers. In several studies, it has been shown to regulate tumor development and progression by acting as a competing endogenous RNA (ceRNA) that “sponges” specific microRNAs, thereby modulating the expression of critical downstream targets involved in cell proliferation, migration, invasion, epithelial‐to‐mesenchymal transition, and drug resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn glioma, MIR9‐2HG was found to be markedly upregulated and predominantly cytoplasmic, where it binds to miR‑411‑5p. This interaction leads to increased expression of topoisomerase 2 alpha (TOP2A), promoting cell proliferation and supporting an oncogenic role."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in hepatocellular carcinoma, MIR9‐2HG exerts its effect by binding to miR‑149‑5p, thereby modulating LRIG2 expression and associating with advanced stage, metastasis, and an unfavorable prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn breast cancer and non‐small cell lung cancer, MIR9‐2HG contributes to tumor progression through additional ceRNA mechanisms. In breast cancer, it sequesters miR‑30a‑5p, leading to enhanced integrin β3 (ITGB3) expression and activation of downstream signaling pathways that drive migratory and invasive behavior."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In non‐small cell lung cancer, MIR9‐2HG interacts with miR‑4478 to upregulate E2F1 expression, while further studies identified a LINC00461/miR‑518a‑3p/WDR1 axis that underscores its pro‐tumorigenic role in this disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn rectal cancer and lung adenocarcinoma, MIR9‐2HG has been implicated in chemoresistance and enhanced tumor aggressiveness. In rectal cancer, its regulation of the miR‑593‑5p/cyclin D1 (CCND1) axis underlies resistance to cisplatin and promotes cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In lung adenocarcinoma, it negatively regulates miR‑195, which in turn leads to the upregulation of HOXA10 and other invasion‐related genes, thereby facilitating cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional evidence from renal cell carcinoma, gastric cancer, and even myocardial ischemia‐reperfusion injury further supports the broad impact of MIR9‐2HG in pathophysiological settings. In renal cell carcinoma, MIR9‐2HG appears to act as a ceRNA influencing key genes such as SALL1, METAP1, and DCAF11 to affect drug resistance and patient survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Its role in gastric cancer, linked to the regulation of LSD1, and in myocardial ischemia‐reperfusion injury through the miR‑185‑3p/Myd88 axis, underscores its diverse regulatory capacity beyond oncogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S Deguchi, K Katsushima, A Hatanaka, et al. 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