{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long intergenic non‐coding RNA 00963 (LINC00963) has emerged as an important regulator in diverse pathological contexts, most notably in cancer. Elevated LINC00963 expression has been observed in non‐small cell lung cancer where its high levels correlate with poor prognosis by promoting cell migration and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In prostate cancer, LINC00963 drives the transition from androgen‐dependent to more aggressive castration‐resistant disease by enhancing proliferation and metastasis through modulation of the EGFR signaling pathway and induction of epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Similarly, in esophageal squamous cell carcinoma and colorectal cancer, LINC00963 functions as a competing endogenous RNA by sponging tumor‐suppressive microRNAs (e.g. miR‑214‑5p, miR‑10b, miR‑1281, or miR‑532‑3p), thereby upregulating oncogenic targets that enhance proliferation, invasion, and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In gastric cancer, its upregulation contributes to chemoresistance by promoting autophagy via a miR‑4458/ATG16L1 axis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while in bladder cancer, LINC00963 enhances malignant phenotypes through regulation of the miR‑766‑3p/MTA1 pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Outside the realm of traditional tumors, aberrant LINC00963 expression has also been linked to non-malignant conditions such as pulmonary arterial hypertension, where it modulates smooth muscle cell proliferation and migration via the miR‑328‑3p/PFN1 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Mechanistically, LINC00963 generally operates by “sponging” specific microRNAs, thereby de-repressing downstream oncogenes or effectors (e.g. TRIM65 in colorectal cancer) and activating key signaling cascades including PI3K/AKT, EGFR, JAK2/STAT1, and pathways underlying epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these findings indicate that LINC00963 acts as a pleiotropic driver of tumor progression and drug resistance across multiple cancer types, positioning it as a promising prognostic biomarker and potential therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tao Yu, Yingjun Zhao, Zhixiang Hu, et al. 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