{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA HEIH has emerged as an oncogenic regulator in multiple malignancies. In hepatitis B virus–related hepatocellular carcinoma, HEIH is highly expressed and its upregulation is associated with tumor recurrence, poor survival, and cell cycle dysregulation via binding to the polycomb repressor EZH2 to repress its target genes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In colorectal cancer, HEIH promotes proliferation by binding to microRNAs (e.g., miR‐939) and thereby preventing their inhibition of key prosurvival factors such as NF‐κB–mediated Bcl‐xL expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in triple‐negative breast cancer HEIH is overexpressed and functions as a competing endogenous RNA (ceRNA), sequestering miR‐4458 to modulate the SOCS1 axis and influencing cell proliferation and apoptosis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", with additional evidence in breast cancer underscoring its association with advanced malignancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In melanoma and other tumor models, HEIH appears consistently upregulated where it contributes to increased cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In endometrial cancer, HEIH overexpression is linked to chemoresistance through activation of the MAPK pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and in cholangiocarcinoma it exerts oncogenic effects through a ceRNA network involving miR‐98‐5p and the upregulation of HECTD4."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In esophageal squamous cell carcinoma, HEIH associates with EZH2 to repress TP53 expression, thereby contributing to a more aggressive phenotype"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while in nasopharyngeal carcinoma HEIH functions as a molecular sponge for miR‐193a‐5p, leading to CDK8 upregulation and enhanced cellular progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In gastric cancer, elevated HEIH levels correlate with larger tumor size, metastatic features, and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies indicate that HEIH is consistently upregulated across diverse cancer types, where it drives tumor progression through multiple mechanisms including (a) binding to chromatin modifiers like EZH2 to suppress tumor‐suppressor genes; (b) acting as a competing endogenous RNA to sequester tumor‐suppressive miRNAs; and (c) modulating key signaling pathways involved in proliferation, apoptosis, metastasis, and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "9"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fu Yang, Ling Zhang, Xi-song Huo, et al. 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