{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNUDCD1, also known as CML66 or OVA66, is emerging as a multifunctional oncoprotein whose deregulated expression plays significant roles in tumor biology. Initial studies identified alternative isoforms generated via alternative promoter usage and splicing, with distinct N‐ and C‐terminal regions leading to differential tissue expression and epitope generation. One isoform, predominantly expressed in testis and minimally in tumors, contrasts with a longer isoform expressed in both tumors and testis, suggesting that alternative splicing and promoter regulation are key mechanisms in controlling its antigenicity and immune recognition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFunctional studies in cervical carcinoma have demonstrated that knockdown of CML66/NUDCD1 reduces cell proliferation, migration, invasion, and even metastatic potential in vivo, with concomitant downregulation of key metastasis-associated genes. Similar results from ovarian cancer models indicate that elevated expression stimulates proliferation, survival, and angiogenesis by interfacing with autocrine VEGF–VEGFR2 signaling, while its ability to elicit spontaneous humoral and cellular immune responses positions it as a promising immunotherapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, detailed analyses of NudCD1 have revealed its complex expression patterns across normal and cancer tissues. Its mRNA is found in normal heart and testis but is overexpressed in numerous cancers. The protein exists as multiple isoforms with distinct subcellular localizations – with one isoform localizing to the nucleus and others exhibiting both cytoplasmic and nuclear distributions – and engaging unique interaction partners (for instance, binding to the RNA helicase DHX15 involved in mRNA splicing). These findings suggest that alternative splice isoforms may underpin distinct functional roles in tumor development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNUDCD1 also appears to contribute to tumor progression in renal cell carcinoma and non‐small cell lung cancer. Studies show that its overexpression correlates with increased proliferation, migration, and invasion of cancer cells, and its aberrant levels have been proposed as potential markers for early detection and disease progression evaluation in renal cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, in colorectal cancer models, enforced expression of NUDCD1 disrupts the spindle assembly checkpoint and modulates the expression of key regulatory genes involved in mitosis, such as BUB1 and MAD1, eventually influencing cell cycle progression and apoptosis. Complementary pan-cancer analyses have revealed that NUDCD1 is broadly overexpressed, is linked with several genetic and epigenetic alterations, and associates with immune checkpoint molecules as well as drug sensitivity profiles, thereby underscoring its multifaceted role in tumorigenesis and potential as a target in personalized cancer therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yan Yan, Leuyen Phan, Fan Yang, et al. 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