{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA “cancer susceptibility candidate 2” (CASC2) has emerged as an important regulatory molecule in both tumorigenesis and other pathological conditions. In the vast majority of studies, CASC2 is significantly downregulated in a wide range of human cancers – including hepatocellular carcinoma, glioma, colorectal cancer, renal cell carcinoma, bladder cancer, non‐small cell lung cancer, osteosarcoma, breast cancer, gastric cancer, pancreatic cancer and prostate cancer – where its loss correlates with advanced disease stage, metastasis and poorer overall prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": " \n Functionally, forced expression of CASC2 in these systems suppresses cell proliferation, migration and invasion, promotes cell cycle arrest and induces apoptosis both in vitro and in vivo."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, CASC2 typically acts as a competing endogenous RNA (ceRNA) by “sponging” several oncogenic microRNAs – including miR‐367, miR‐21, miR‐181a, miR‐18a, miR‐193a‐5p and miR‐24–3p – to derepress key tumor suppressor genes such as FBXW7, PIAS3, PTEN, RASSF6, and others, thereby modulating critical signaling pathways (for example, NF‐κB, MAPK, PI3K/AKT, and Wnt/β‐catenin) that govern cell survival, proliferation and invasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "19"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In several tumor types, CASC2 upregulation can also modulate chemoresponsiveness – for example, increasing sensitivity to temozolomide in glioma and to paclitaxel or docetaxel in breast and prostate cancers, respectively – highlighting its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " \n Moreover, outside of oncology, reduced CASC2 levels have been associated with chronic complications such as diabetic nephropathy and chronic renal failure, where its serum expression may serve as a diagnostic biomarker"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": ", and diminished CASC2 expression in pulmonary arterial smooth muscle cells contributes to vascular remodeling in pulmonary arterial hypertension."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Notably, while the bulk of evidence supports a tumor‐suppressive role for CASC2, certain reports have identified context‐dependent or variant isoforms (for example, a CASC2 variant referred to as CASC2c in astrocytoma) that may exhibit oncogenic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": " Collectively, these studies underscore the multifaceted role of CASC2 in cell fate determination, chemoresistance and disease progression, supporting its further development as both a prognostic biomarker and a therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yufeng Wang, Zhikui Liu, Bowen Yao, et al. 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