Regulation of mRNA translation by eIF5B in head and neck squamous cell carcinoma (HNSCC)

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Muley, Rachana
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta. : University of Lethbridge, Dept. of Chemistry & Biochemistry
Studies have demonstrated that eIF5B promotes cap-independent translation of the anti-apoptotic factor, XIAP, under stress conditions. Also, eIF5B depletion results in the decreased levels of several pro-survival proteins, thus sensitizing glioblastoma cells to TRAIL-induced apoptosis. Here, we have shown high EIF5B mRNA expression in HNSCC was associated with poor patients’ survival. Further, to assess the impact of eIF5B on HNSCC biology, we depleted eIF5B in three HNSCC cell lines. We also show that eIF5B depletion enhanced the sensitivity of Cal-33 and UM-SCC-29 cells to TRAIL-induced apoptosis. Further, we show the levels of anti-apoptotic proteins Bcl-xL, cIAP1, cFLIPs, and XAIP were decreased upon eIF5B depletion in Cal-33 suggesting the role of eIF5B in the translation of these proteins which was further supported by our polysome profiling data. Altogether our findings suggest that eIF5B may play an important role in the translation of mRNAs encoding key anti-apoptotic proteins that evade apoptosis.
Cancer -- Gene therapy , Cancer -- Treatment , Cancer genes , Glioblastoma multiforme , Squamous cell carcinoma