EIF5A2 (Eukaryotic Translation Initiation Factor 5A2)

We show how the loss of activity of the translation initiation factor EIF5A2-either through gene hypermethylation or pharmacologic inhibition of its highly specific hypusine post-translational modification-induces venetoclax sensitivity in acute myeloid leukaemia (AML) cells.

The high EIF5A2 expression group was more sensitive to cisplatin, crizontinib, gemcitabine, and nilotinib in LIHC. High EIF5A2 expression was associated with several pathways, including cell cycle, proteasome, DNA replication, primary immunodeficiency and oocyte meiosis. EIF5A2 may serve as a potential prognostic marker and a latent focus for cancer immunological treatment.

In addition, polyamines upregulated the expression of five ribosomal proteins, particularly RPS27A, RPL36A, and RPL22L1, which are associated with cancer malignancy. Our findings reveal an important role for eIF5A2, regulated by polyamines and miR-6514-5p, in cancer cell proliferation, suggesting that the interaction between eIF5A2 and ribosomes, which regulate cancer progression, is a selective target for cancer treatment.

Our data identified a novel molecular pathway comprising the METTL3-m6A-TUG1-miR-9-EIF5A2 signaling axis in HCC, providing new targets for future DOX resistance management.

Supervised analysis, employing regularized Cox regression, identified 12 genes (CHRDL2, SPP2, VAC14, IRF5, GUCY1B1, NCS1, RRM2B, EIF5A2, CCDC62, CTCFL, XG, and TP53INP2) whose weighted degree in SSNs is predictive of patient survival in LUAD. These findings suggest that topological features of SSNs offer valuable insights into the context-specific nature of LUAD malignancy, highlighting the potential of SSN-based approaches for further research.

We also elucidate the molecular mechanisms associated with EIF5A2 in the context of tumorigenesis and drug resistance. We propose that the biological roles of EIF5A2 in regulating diverse cellular processes and tumorigenesis are clinically significant and warrant further investigation.

JDK and Quercetin inhibited OSF carcinogenesis by inhibiting the AR/eIF5A2 signal-mediated EMT.

In contrast, overexpression of eIF5A2 abolished the anti-tumor effects of TRIM71. In summary, TRIM71 may exert its anti-tumor effects through regulating eIF5A2, highlighting the potential of TRIM71 as an effective therapeutic target for the treatment of LSCC.

Immunoinfiltration analysis showed that M0 macrophage abundance was correlated with the prognosis of HCC patients. Immunohistochemistry revealed differences in DHX58 and EIF5A2 expression between HCC tissues with and without extrahepatic metastasis, consistent with our bioinformatics findings.

Our results demonstrate the value of consideration of RBP in the diagnosis and prognosis for HNSCC and provide a novel insight into understanding the potential role of dysregulated RBP in HNSCC.

In solid tumors, EIF5A2 emerges as a reliable prognostic marker. Our meta-analysis comprehensively analyzed the prognostic value of EIF5A2 in solid tumors and assessed its efficacy as a predictive marker.

Consistent with this, organoids with high levels of EIF5A2 were sensitive to AKT inhibitors. Our study identified novel genes that promote prostate cancer formation through upregulation of the PI3K pathway, predicting a strategy to treat patients with genetic aberrations in these genes particularly relevant for EIF5A2 amplified tumours.