{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Eukaryotic translation initiation factor 5A2 (EIF5A2) is a specialized isoform of the essential translation factor eIF5A that is normally expressed only in select tissues but is frequently upregulated in a wide range of human cancers. Gene amplification of the 3q26 region—a frequent event in several malignancies—often leads to EIF5A2 overexpression, which correlates with increased tumor cell migration, invasion, and metastasis. In colorectal, hepatocellular, ovarian, non‐small cell lung, gastric, bladder, and pancreatic cancers, elevated EIF5A2 levels have been associated with aggressive clinicopathologic features, enhanced epithelial‐to‐mesenchymal transition (EMT), adverse patient prognosis, and chemoresistance ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Mechanistically, EIF5A2 promotes tumor progression by modulating multiple oncogenic pathways. It can stimulate cytoskeletal reorganization and activate small GTPases, thereby enhancing cell motility and invasion ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. In several cancers, EIF5A2 upregulation induces EMT through down‐regulation of epithelial markers and up‐regulation of mesenchymal proteins, often by transcriptional activation of metastasis‐associated genes such as MTA1 or through enhanced TGF‐β1 expression mediated by stabilization and nuclear translocation of STAT3 ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]. In addition, EIF5A2 has been implicated in metabolic reprogramming in hepatocellular carcinoma, where it promotes glucose uptake, lactate secretion, and lipogenesis, underscoring its role in rewiring cancer cell metabolism ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Multiple lines of evidence further indicate that EIF5A2 contributes to chemoresistance. In bladder and hepatocellular carcinoma cells, inhibition of EIF5A2—either via small interfering RNA or by targeting its unique posttranslational hypusination (using agents such as GC7)—sensitizes cancer cells to chemotherapeutic drugs, thereby reversing the EMT phenotype and reducing tumor aggressiveness ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Regulatory mechanisms upstream of EIF5A2 further highlight its importance in cancer biology. Several microRNAs—including miR‐203, miR‐125b, miR‐30b, miR‐221–3p, and miR‐383—have been shown to directly target the EIF5A2 mRNA, thereby suppressing its translation and attenuating its oncogenic effects. Loss or downregulation of these miRNAs has been observed in colorectal, gastric, hepatocellular, and medulloblastoma cells, contributing to the unchecked expression of EIF5A2 and promoting tumor progression and chemoresistance ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "].\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies establish EIF5A2 as a multifaceted oncogenic protein whose aberrant activation via gene amplification and/or loss of regulatory microRNAs drives tumor cell proliferation, invasion, EMT, and chemoresistance. Its pivotal role in controlling key translational and metabolic processes makes EIF5A2 a promising prognostic biomarker and a potential therapeutic target across diverse cancer types ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "19"}]}, {"type": "t", "text": "].\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Zhu, Mu-Yan Cai, Zhu-Ting Tong, et al. 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