Eif5a2, the eukaryotic initiation factor 5A2 gene, is a highly conserved and multifunctional gene. It significantly influences various cellular processes such as translation elongation, RNA binding, ribosome binding, protein binding, and post-translational modifications. It is involved in multiple molecular pathways, with its overexpression frequently observed in multiple cancers where it functions as an oncoprotein, and also implicated in drug resistance [1].

Eif5a2-related functional studies show that its knockdown in various cancer cell lines leads to significant impacts. In intrahepatic cholangiocarcinoma cells, high levels of Eif5a2 promote cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR signaling pathway [2]. In epithelial ovarian cancer cells, knockdown of Eif5a2 reduces the expression of stem-related markers, inhibits self-renewal ability, improves chemosensitivity, and inhibits tumorigenesis in vivo, indicating its positive regulation of stemness via the E2F1/KLF4 pathway [3]. In cervical cancer cells, Eif5a2 knockdown inhibits cell proliferation, migration, and invasion, promotes apoptosis, and enhances cisplatin sensitivity, with its effect mediated through AGR2 [4]. In bladder cancer cells, Eif5a2 promotes doxorubicin resistance through the TGF-β signaling pathway, and its knockdown reverses this effect [5]. In ovarian cancer, knockout of Eif5a2 inhibits epithelial-to-mesenchymal transition (EMT), cell migration, invasion, tumor growth, and metastasis, while overexpression promotes these processes by activating the TGFβ pathway [6]. In oral cancer SCC-9 cells, targeting Eif5a2 reduces invasion and migration, promotes apoptosis, increases chemosensitivity, and upregulates Bim and E-cadherin [7]. In anaplastic thyroid carcinoma, targeting Eif5a2 with shRNA induces cell death in vitro and in vivo, downregulating p-Smad2/3, while overexpression promotes cell growth and upregulates p-Smad3 [8].

In conclusion, Eif5a2 is a crucial gene involved in multiple cellular regulatory processes and plays a significant role in tumorigenesis and drug resistance in various cancers. Gene knockout and knockdown models in cancer cell lines and in vivo mouse models have revealed its functions in promoting cancer cell proliferation, invasion, metastasis, stemness, and drug resistance through different signaling pathways, providing potential therapeutic targets for cancer treatment.