{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The coiled‐coil domain containing 66 (CCDC66) locus has been implicated in a wide array of cellular functions in both its protein‐coding and circular RNA [circCCDC66] forms. On one hand, studies have demonstrated that circCCDC66 acts as an oncogenic noncoding RNA in several cancers. In colorectal cancer, for instance, circCCDC66 is upregulated and promotes key malignant processes such as cell proliferation, migration, invasion, anchorage‐independent growth, and metastasis by regulating subsets of oncogenes—functions further confirmed in xenograft models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, in non‐small cell lung cancer, elevated levels of circCCDC66—in part regulated by factors such as FAK, c‐Met, and STAT3—drive epithelial‐to‐mesenchymal transition and resistance to drug treatment via the miR‐33a-5p/KPNA4 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In gastric and renal carcinomas, circCCDC66 similarly acts by sponging specific microRNAs (e.g. miR-1238-3p, miR-370) to upregulate oncogenic effectors (e.g. LHX2, MDM4) and enhance cancer stem cell enrichment through the hepatocyte growth factor/c-Met pathway."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " In addition, circCCDC66 has been reported to modulate the proliferation and survival of vascular smooth muscle cells—thereby contributing to vascular pathologies such as abdominal aortic aneurysm—through a miR-342-3p/host gene regulatory mechanism"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and it has been shown to impact enteric cell behavior in Hirschsprung’s disease by sponging miR-488-3p to control DCX expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n On the other hand, the CCDC66 protein is emerging as a critical factor in the organization of membrane-less cellular structures. It has been identified as a microtubule-associated protein that dynamically localizes to centrosomes, centriolar satellites, and primary cilia. Through interactions with key centrosomal components such as CEP72, CEP290, and PCM1, CCDC66 is required for proper centrosome targeting, ciliogenesis, and the maintenance of satellite integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Furthermore, loss-of-function studies in animal models have revealed that disruption of CCDC66 expression in the retina leads to early and progressive photoreceptor degeneration, underscoring its importance in normal retinal development and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Thus, cumulatively, CCDC66 serves dual roles: as a circRNA that modulates gene expression networks to promote cell proliferation, invasion, and chemoresistance in various cancers and vascular pathologies, and as a protein that is essential for centrosome organization, ciliary assembly, and retinal integrity. These multifaceted functions highlight CCDC66 as a promising biomarker and potential therapeutic target in oncology, vascular disease, and retinal degeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kuei-Yang Hsiao, Ya-Chi Lin, Sachin Kumar Gupta, et al. 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