{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n In diverse malignancies, the long non‐coding RNA CRNDE has emerged as a multifaceted oncogenic regulator that modulates key cellular processes via several mechanisms. In uveal melanoma, for example, aberrant alternative splicing of CRNDE transcripts is linked to SF3B1 mutations, suggesting a contribution to splicing deregulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In glioma, CRNDE is upregulated and promotes cell proliferation, migration, and tumor growth through mTOR‐dependent pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In colorectal cancer, nuclear CRNDE transcripts are regulated by insulin/IGF signaling, thereby influencing metabolic reprogramming toward the Warburg effect."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n CRNDE frequently acts as a competing endogenous RNA (ceRNA) to sequester microRNAs and de‐repress oncogenic targets. For instance, in multiple myeloma CRNDE functions as a molecular sponge for miR‑451 to enhance proliferation and anti‑apoptotic capacity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", while in gastric cancer its interaction with splicing regulatory proteins (e.g., SRSF6) modulates alternative splicing events and autophagy, thereby impacting chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In colorectal cancer, CRNDE binds miR‑217 to upregulate TCF7L2 and activate Wnt/β‑catenin signaling, fostering cell proliferation, migration, and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Similar ceRNA‐driven regulation is observed in other cancers; in osteosarcoma, CRNDE promotes proliferation, invasion, and epithelial–mesenchymal transition via activation of the Wnt/β‑catenin pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while in non‐small cell lung cancer it sponges miR‑641 to elevate CDK6 expression, thereby promoting proliferation and suppressing apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In inflammatory settings, CRNDE contributes to disease progression by enhancing colonic epithelial apoptosis through a miR‑495/SOCS1 axis in inflammatory bowel disease"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "and by aggravating sepsis‑induced acute kidney injury via activation of the TLR3/NF‑κB pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In hepatocellular carcinoma, CRNDE sequesters miR‑337‑3p to elevate SIX1 expression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and in cervical cancer its function as a ceRNA is further exemplified by interactions with miR‑183 to upregulate CCNB1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "as well as by binding with PUMA to promote cell growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Collectively, these studies underscore that CRNDE exerts its oncogenic role by modulating alternative splicing and functioning as a ceRNA in a context‐dependent manner, thereby promoting tumor cell proliferation, migration, metabolic reprogramming, and resistance to apoptosis. Its multifaceted functions position CRNDE as a promising diagnostic biomarker and therapeutic target across a range of cancers and related diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Simon J Furney, Malin Pedersen, David Gentien, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SF3B1 mutations are associated with alternative splicing in uveal melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Discov (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/2159-8290.CD-13-0330"}], "href": "https://doi.org/10.1158/2159-8290.CD-13-0330"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23861464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23861464"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yunliang Wang, Yutong Wang, Jinfeng Li, et al. 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