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High-risk human papillomavirus-18 uses an mRNA sequence to synthesize oncoprotein E6 in tumors

2021/10/06 by Alejandra García, Giovanna Maldonado, José L. González +8 · 6 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Cervical Cancer and HPV Research #Virus-based gene therapy research #RNA Research and Splicing

paper · doi:10.1073/pnas.2108359118

Abstract

Significance Cervical cancer is the fourth most common cancer in women for both incidence and mortality worldwide. The causal agent is a group of viruses termed high-risk human papillomavirus (HPV). Viral types 16 and 18 cause ∼70% of this burden disease. HPV E6 is a potent oncoprotein that plays a central role in carcinogenesis, but its synthesis remains poorly understood at the level of mRNA translation. We discovered that in cervical tumors, mRNAs possessing 5′ UTRs of 0 to 5 nucleotides and harboring the motif ACC aug GCGCG(C/A)UUU control E6 mRNA translation. This process is highly dependent on eIF4E and eIF4AI, two translation factors linking translation and cancer. We suggest the use of drugs targeting these factors as antineoplasic compounds for HPV-caused cancers.

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