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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Krassnig, S; Wohlrab, C; Golob-Schwarzl, N; Raicht, A; Schatz, C; Birkl-Toeglhofer, AM; Skofler, C; Gantenbein, N; Leoni, M; Asslaber, M; Leber, SL; Mahdy-Ali, K; von Campe, G; Mayer, M; Borenich, A; Weis, S; Benesch, M; Haybaeck, J.
A Profound Basic Characterization of eIFs in Gliomas: Identifying eIF3I and 4H as Potential Novel Target Candidates in Glioma Therapy.
Cancers (Basel). 2021; 13(6): Doi: 10.3390/cancers13061482 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Führende Autor*innen der Med Uni Graz
Haybäck Johannes
Kraßnig Stefanie
Co-Autor*innen der Med Uni Graz
Asslaber Martin
Benesch Martin
Birkl-Töglhofer Anna Maria
Borenich Andrea
Gantenbein Nadine
Golob-Schwarzl Nicole
Leber Stefan
Leoni Marlene
Mayer Marlene
Skofler Christina
von Campe Gord
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Abstract:
Glioblastoma (GBM) is an utterly devastating cerebral neoplasm and current therapies only marginally improve patients' overall survival (OS). The PI3K/AKT/mTOR pathway participates in gliomagenesis through regulation of cell growth and proliferation. Since it is an upstream regulator of the rate-limiting translation initiation step of protein synthesis, controlled by eukaryotic initiation factors (eIFs), we aimed for a profound basic characterization of 17 eIFs to identify potential novel therapeutic targets for gliomas. Therefore, we retrospectively analyzed expressions of mTOR-related proteins and eIFs in human astrocytoma samples (WHO grades I-IV) and compared them to non-neoplastic cortical control brain tissue (CCBT) using immunoblot analyses and immunohistochemistry. We examined mRNA expression using qRT-PCR and additionally performed in silico analyses to observe the influence of eIFs on patients' survival. Protein and mRNA expressions of eIF3B, eIF3I, eIF4A1, eIF4H, eIF5 and eIF6 were significantly increased in high grade gliomas compared to CCBT and partially in low grade gliomas. However, short OS was only associated with high eIF3I gene expression in low grade gliomas, but not in GBM. In GBM, high eIF4H gene expression significantly correlated with shorter patient survival. In conclusion, we identified eIF3I and eIF4H as the most promising targets for future therapy for glioma patients.

Find related publications in this database (Keywords)
diffuse astrocytoma
anaplastic astrocytoma
glioblastoma
eukaryotic initiation factors (eIFs)
mTOR signaling
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