{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nYBX3—also known as ZONAB, DbpA, or CSDA—is a multifunctional nucleic acid–binding protein that regulates cell proliferation and differentiation via transcriptional mechanisms. In epithelial cells, YBX3 shuttles between tight junctions and the nucleus where it directly modulates the expression of key cell cycle regulators such as cyclin D1 and proliferating cell nuclear antigen, thereby promoting the G1/S-phase transition. Furthermore, YBX3 contributes to cellular stress responses by binding to the 3′‐untranslated region of p21 mRNA to stabilize and enhance its translation, linking junctional signals to cell survival. These transcriptional regulatory roles have been described in studies investigating the control of proliferation and differentiation in various epithelial contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its transcriptional functions, YBX3 acts as a critical RNA‐binding protein that posttranscriptionally regulates gene expression. It stabilizes specific messenger RNAs such as those encoding amino acid transporters (e.g., SLC7A5, SLC3A2, and SLC1A5) and factors involved in growth factor signaling. Moreover, YBX3 participates in the formation of multiprotein ribonucleoprotein complexes that influence mRNA stability, with evidence pointing to its involvement in the regulation of vascular endothelial growth factor mRNA. Recent investigations have also revealed that long noncoding RNAs—including HEIH and BLACAT3—can interact with and modulate YBX3 function, thereby impacting tumor immune evasion and metastatic processes, as well as affecting differentiation programs in skeletal muscle."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of YBX3 has been implicated in the pathogenesis and progression of multiple cancers. In colorectal, hepatocellular, and gastric cancers, altered YBX3 (or dbpA) expression correlates with enhanced proliferation, invasion, and resistance to chemotherapeutics—a link that has been further supported by gene knockdown studies showing cell cycle arrest, increased apoptosis, and inhibition of oncogenic signaling pathways (such as MAPK and Wnt/β‐catenin/Chk1). YBX3 overexpression has also been reported in clear cell renal cell carcinoma, where it serves as a prognostic indicator and is associated with immune cell infiltration. Additionally, YBX3 appears capable of restraining influenza A virus replication by disrupting vRNP complex activity, and its upregulation fosters invasive properties in bladder cancer by modulating epithelial–mesenchymal transition. Collectively, these findings position YBX3 as an important therapeutic target as well as a potential biomarker for tumor progression and treatment response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tony Sourisseau, Anastasios Georgiadis, Anna Tsapara, et al. 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