Authors:

Belle L. Lewis

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About Paper:

Prostate cancer remains a leading cause of cancer-related mortality among men. SELENOF, a selenoprotein critical for protein quality control, is significantly reduced in prostate cancer, and its loss is linked to aggressive disease phenotypes. SELENOF translation requires UGA codon recoding mediated by the SECIS element in the 3'UTR of its mRNA. elF4a3 is an RNA-binding protein involved in RNA splicing and translational control of selenoproteins like glutathione peroxidase 1 by binding onto its mRNA, a mechanism that also extends to SELENOF. Binding of elF4a3 to SELENOF mRNA reduces its translation, leading to its low levels in cancer. Previous studies show elF4a3 inhibition restores SELENOF levels, but global inhibition is cytotoxic and non-specific. This study introduces a novel strategy using synthetic RNA decoy oligonucleotides designed to selectively block elF4a3 interaction with SELENOF mRNA without broadly interfering with its other biological functions. Using a dual-luciferase reporter system, we measured UGA readthrough efficiency in PC3, human prostate cancer cells, treated with RNA decoys. SELENOF protein and mRNA levels were measured by Western blotting and RT-PCR. Our results show that RNA decoys significantly increase luciferase activity and SELENOF protein levels in a dose-dependent manner, while mRNA levels remain unchanged, confirming post-transcriptional regulation. These findings support RNA decoys as a promising therapeutic approach to restore SELENOF levels and reverse cancer-associated phenotypes. Future studies will optimize decoy design and in vivo efficacy, paving the way for targeted RNA-based therapies in prostate cancer.

Source:

DePaul University

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Co-authors:

Belle L. Lewis