Inhibiting eukaryotic initiation factor 5A (eIF5A) hypusination attenuated activation of the SIK2 (salt-inducible kinase 2)-p4E-BP1 pathway involved in ovarian cancer cell proliferation and migration.

Background: Eukaryotic initiation factor 5A hypusine (eIF5A) stimulates the translation of proline repeat motifs. Salt inducible kinase 2 (SIK2) containing a proline repeat motif is overexpressed in ovarian cancers, in which it promotes cell proliferation, migration, and invasion.

Methods And Results: Western blotting and dual luciferase analyses showed that depletion of eIF5A by GC7 or eIF5A-targeting siRNA downregulated SIK2 level and decreased luciferase activity in cells transfected with a luciferase-based reporter construct containing consecutive proline residues, whereas the activity of the mutant control reporter construct (replacing P825L, P828H, and P831Q) did not change.

Eukaryotic initiation factor 5A hypusine as a negative regulator of adenosine 2B receptor (A2bAR) through interaction with stem loop sequences within the A2bAR 3'-untranslated region.

Purpose: The aim of this study was to investigate whether eIF5A hypusine (eIF5A) reduces adenosine 2b receptor (A2bAR) gene expression through interaction with highly structured stem-loop sequences within the A2bAR 3'UTR.

Methods And Results: Based on real-time PCR and western blotting, expression of A2bAR mRNA was significantly decreased upon treatment with eIF5A in mouse embryonic fibroblasts of eIF5A (eIF5A-MEF) and 3T3-L1 cells. Target Scan software and RNAfold web server predicted two different structures formed by stem-loop sequences with overlapping microRNA 27 seed sequences and mutations.