{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n This abstract summarizes the multifaceted roles of the long non‐coding RNA CPS1 intronic transcript 1 (CPS1‑IT1) in cancer and related disease processes. In several solid tumors – including colorectal cancer (CRC), hepatocellular carcinoma (HCC), melanoma, glioma, epithelial ovarian cancer (EOC), and lung cancer – CPS1‑IT1 is generally downregulated, and low expression levels are associated with enhanced cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and overall poor clinical outcomes. For example, in CRC, CPS1‑IT1 suppresses EMT and autophagy by inhibiting the activation of hypoxia‑inducible factor‑1α (HIF‑1α), thereby reducing tumor metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In HCC and melanoma, CPS1‑IT1 acts as a tumor suppressor by attenuating HIF‑1α signaling – either directly or indirectly via modulation of factors such as Hsp90 or by upregulating transcription factors like FOXA2 – resulting in decreased EMT progression and metastatic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " In glioma, enforced expression of CPS1‑IT1 reduces cell proliferation, migration, and invasion, supporting its role as an inhibitor of tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, in lung cancer and EOC, restoration of CPS1‑IT1 expression suppresses tumor cell growth and invasion while promoting apoptotic pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In contrast, studies in intrahepatic cholangiocarcinoma (ICC) have revealed that CPS1‑IT1, together with its partner gene CPS1, is upregulated; in this context, its elevated expression correlates with enhanced cell proliferation, poorer liver function, and reduced survival"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", indicating that CPS1‑IT1 may exert context‐dependent functions.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, beyond its role in cancer, CPS1‑IT1 has been implicated in non‑malignant pathological processes. In a rat model of pulmonary arterial hypertension, for instance, overexpression of CPS1‑IT1 alleviated disease features by reducing IL‑1β expression via inhibition of HIF‑1 transcriptional activity and interference with the NF‑κB signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that CPS1‑IT1 predominantly functions as a tumor suppressor – largely by mitigating HIF‑1α activation and EMT – in a variety of cancers, although its role may vary in a tissue‐specific manner. The modulation of CPS1‑IT1 expression thus holds promise not only as a prognostic biomarker but also as a potential therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Zhang, Weitang Yuan, Junmin Song, et al. 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