{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA CASC15 has emerged as a multifunctional oncogenic regulator in a spectrum of human diseases. In hematologic malignancies, CASC15 has been shown to modulate the expression of nearby genes such as SOX4, thereby affecting cellular survival, proliferation, and differentiation in RUNX1‐translocated leukemia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In solid tumors including metastatic melanoma, gastric cancer, colon cancer, cervical cancer, ovarian cancer, intrahepatic cholangiocarcinoma, and neuroblastoma, CASC15 is frequently upregulated and associated with aggressive disease features and poor prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, CASC15 exerts its oncogenic functions through multiple complementary routes. It acts as a competing endogenous RNA by “sponging” microRNAs—for instance, miR‑4310 in colon cancer, miR‑33a‑5p in hepatocellular carcinoma, and miR‑365 in laryngeal and other cancers—thereby relieving the inhibition on downstream oncogenes (e.g., LGR5, TWIST1, cyclin D1) and activating critical signaling pathways such as Wnt/β‑catenin and PI3K/AKT."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, CASC15 interacts with chromatin‐modifying factors (for example, EZH2 and WDR5) to control transcription of cell cycle inhibitors such as CDKN1A, and modulates the stability of key oncoproteins like MYCN via regulation of deubiquitinases such as USP36."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its roles in cancer, aberrant CASC15 expression has been implicated in other disease contexts. For example, in diabetic patients with chronic renal failure, high-glucose conditions induce CASC15 upregulation in podocytes, where it promotes apoptosis by sponging miR‑34c."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore that CASC15 functions as a versatile oncogenic long noncoding RNA. By modulating microRNA activity, epigenetic regulators, and key signaling cascades, CASC15 contributes to tumor initiation, progression, metastatic potential, and treatment resistance across multiple tumor types. Its consistent association with poor clinical outcomes marks CASC15 as a promising diagnostic biomarker and potential therapeutic target in cancer and other pathological conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thilini R Fernando, Jorge R Contreras, Matteo Zampini, et al. 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