{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA HCG18 has emerged as a multifunctional regulatory RNA whose expression and activity are context‐dependent. In numerous solid tumors—including lung adenocarcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", colorectal cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ", nasopharyngeal carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "and hepatocellular carcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "—HCG18 is frequently upregulated, where it acts as a competing endogenous RNA (ceRNA) by “sponging” specific microRNAs to de‐repress key oncogenic targets. For example, in lung adenocarcinoma HCG18 sequesters miR‑34a‑5p to enhance HMMR expression, whereas in colorectal and nasopharyngeal carcinomas it binds miR‑1271 and miR‑140, respectively, to promote the activation of MTDH/Wnt/β‑catenin signaling and cyclin D1 expression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Similarly, in hepatocellular carcinoma HCG18 functions through the miR‑214‑3p/CENPM axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in various other cancers—including gastric"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", epithelial ovarian"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", pancreatic"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", osteosarcoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", head and neck"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ", and melanoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "—HCG18 modulates diverse downstream effectors (such as NOTCH1, TRAF4/5, EGFR, DDX3X, PGK1, FOXC1, FGFR1, and CDK16) via interactions with microRNAs including miR‑34c‑5p, miR‑29a/b, miR‑197‑3p, miR‑370‑3p, miR‑146a‑5p, miR‑188‑5p and miR‑133b"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": ", and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In contrast, in papillary thyroid carcinoma HCG18 is downregulated and appears to inhibit tumor progression via the miR‑106a‑5p/PPP2R2A axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", highlighting possible tissue‐ or tumor‐specific functions."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond tumor cell–intrinsic roles, HCG18 has been implicated in modulating the tumor microenvironment; for instance, its aberrant expression correlates with increased M2 macrophage infiltration in prostate cancer bone metastases"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "and exosomally delivered HCG18 from gastric cancer cells facilitates M2 polarization via the miR‑875‑3p/KLF4 pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " Moreover, in non‐oncologic contexts, HCG18 participates in inflammatory and degenerative processes such as intervertebral disc degeneration by modulating the miR‑146a‑5p/TRAF6/NF‑κB axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "and may even contribute to immune regulation in Alzheimer’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, current evidence indicates that HCG18 functions primarily as a ceRNA, sequestering various microRNAs to fine‐tune the expression of oncogenes and other regulatory proteins that govern cell proliferation, migration, invasion, metabolic reprogramming, and immune interactions. This multifaceted regulatory role renders HCG18 a promising candidate for the development of novel diagnostic biomarkers and targeted therapeutic strategies in diverse pathological conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "18"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "17"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_fs", "start_ref": "14", "end_ref": "16"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "22"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "24"}, {"type": "fg_f", "ref": "19"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "25"}, {"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Li, Tinghong Pan, Wei Jiang, et al. 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