{"doi":"10.1002/ijc.34545","title":"Deoxyhypusine hydroxylase: A novel therapeutic target differentially expressed in short‐term vs long‐term survivors of glioblastoma","abstract":"<jats:title>Abstract</jats:title><jats:p>Glioblastoma (GB) is the most aggressive neoplasm of the brain. Poor prognosis is mainly attributed to tumor heterogeneity, invasiveness and drug resistance. Only a small fraction of GB patients survives longer than 24 months from the time of diagnosis (ie, long‐term survivors [LTS]). In our study, we aimed to identify molecular markers associated with favorable GB prognosis as a basis to develop therapeutic applications to improve patients' outcome. We have recently assembled a proteogenomic dataset of 87 GB clinical samples of varying survival rates. Following RNA‐seq and mass spectrometry (MS)‐based proteomics analysis, we identified several differentially expressed genes and proteins, including some known cancer‐related pathways and some less established that showed higher expression in short‐term (&lt;6 months) survivors (STS) compared to LTS. One such target found was deoxyhypusine hydroxylase (DOHH), which is known to be involved in the biosynthesis of hypusine, an unusual amino acid essential for the function of the eukaryotic translation initiation factor 5A (eIF5A), which promotes tumor growth. We consequently validated DOHH overexpression in STS samples by quantitative polymerase chain reaction (qPCR) and immunohistochemistry. We further showed robust inhibition of proliferation, migration and invasion of GB cells following silencing of DOHH with short hairpin RNA (shRNA) or inhibition of its activity with small molecules, ciclopirox and deferiprone. Moreover, DOHH silencing led to significant inhibition of tumor progression and prolonged survival in GB mouse models. Searching for a potential mechanism by which DOHH promotes tumor aggressiveness, we found that it supports the transition of GB cells to a more invasive phenotype via epithelial‐mesenchymal transition (EMT)‐related pathways.</jats:p>","journal":"International Journal of Cancer","year":2023,"id":672327,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1756610,"name":"Eilam Yeini","orcid":"0000-0003-3491-3994","position":1,"is_corresponding":false},{"id":1526632,"name":"Gali Arad","orcid":null,"position":2,"is_corresponding":false},{"id":1698374,"name":"Artem Danilevsky","orcid":"0000-0003-3146-7765","position":3,"is_corresponding":false},{"id":693535,"name":"Sabina Pozzi","orcid":"0000-0002-6299-9273","position":4,"is_corresponding":false},{"id":1756611,"name":"Christian Burgos Luna","orcid":null,"position":5,"is_corresponding":false},{"id":1756612,"name":"Sahar Israeli Dangoor","orcid":null,"position":6,"is_corresponding":false},{"id":1756613,"name":"Rachel Grossman","orcid":null,"position":7,"is_corresponding":false},{"id":1756614,"name":"Zvi Ram","orcid":null,"position":8,"is_corresponding":false},{"id":430506,"name":"Noam Shomron","orcid":"0000-0001-9913-6124","position":9,"is_corresponding":false},{"id":225596,"name":"Henry Brem","orcid":"0000-0001-7539-4786","position":10,"is_corresponding":false},{"id":6265,"name":"Thomas M. 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In our study, we aimed to identify molecular markers associated with favorable GB prognosis as a basis to develop therapeutic applications to improve patients' outcome. We have recently assembled a proteogenomic dataset of 87 GB clinical samples of varying survival rates. Following RNA‐seq and mass spectrometry (MS)‐based proteomics analysis, we identified several differentially expressed genes and proteins, including some known cancer‐related pathways and some less established that showed higher expression in short‐term (&lt;6 months) survivors (STS) compared to LTS. One such target found was deoxyhypusine hydroxylase (DOHH), which is known to be involved in the biosynthesis of hypusine, an unusual amino acid essential for the function of the eukaryotic translation initiation factor 5A (eIF5A), which promotes tumor growth. We consequently validated DOHH overexpression in STS samples by quantitative polymerase chain reaction (qPCR) and immunohistochemistry. We further showed robust inhibition of proliferation, migration and invasion of GB cells following silencing of DOHH with short hairpin RNA (shRNA) or inhibition of its activity with small molecules, ciclopirox and deferiprone. Moreover, DOHH silencing led to significant inhibition of tumor progression and prolonged survival in GB mouse models. Searching for a potential mechanism by which DOHH promotes tumor aggressiveness, we found that it supports the transition of GB cells to a more invasive phenotype via epithelial‐mesenchymal transition (EMT)‐related pathways.</jats:p>","is_dataset_classified":null,"base_score":2.302585092994046,"endowment":2.302585092994046,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37141410","pmcid":null,"openalex_id":"https://openalex.org/W4368342752","authors":[],"funders":[{"funder_name":"H2020 European Research Council","grant_id":"835227","title":"Brain metastases: Deciphering tumor-stroma interactions in three dimensions for the rational design of nanomedicines"},{"funder_name":"H2020 European Research Council","grant_id":"862580","title":"Predicting clinical response to anticancer drugs using 3D-bioprinted tumor models for personalized therapy"},{"funder_name":"Israel Cancer Research Fund","grant_id":"ICRF‐PROF‐18‐682","title":null},{"funder_name":"Israel Science Foundation","grant_id":"1969/18","title":null},{"funder_name":"Israel Cancer Research Fund","grant_id":"ICRF-PROF-18-682","title":null},{"funder_name":"Morris Kahn Foundation","grant_id":"","title":null}],"total_grants":6,"fwci":0.8347,"citation_percentile":0.69301194,"influential_citations":0,"citation_trend":[{"year":2024,"count":5},{"year":2025,"count":3},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34545","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.34545","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.34545","host_type":"publisher"},{"url":"https://doi.org/10.1002/ijc.34545","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37141410","host_type":"repository"},{"url":"http://dx.doi.org/10.1002/ijc.34545","host_type":""}],"fields_of_study":["Polyamine Metabolism and Applications","Epigenetics and DNA Methylation","Amino Acid Enzymes and Metabolism","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":["Ciclopirox","Animals","Glioblastoma","Humans","Mixed Function Oxygenases","Survivors","Mice"],"keywords":["Gene silencing","Biology","Small hairpin RNA","Cancer research","RNA interference","Translation (biology)","Proteomics","Cancer","RNA","Messenger RNA","Gene","Genetics","Glioblastoma","Proteogenomics","Long-term Survivors","Short-term Survivors","Deoxyhypusine Hydroxylase (Dohh)","Mice","Animals","Humans","Survivors","Ciclopirox","Mixed Function Oxygenases"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T08:40:31.186083Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}