Abstract
Infections with high-risk human papillomaviruses cause ~5% of all human cancers. E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance. E6 and E7 encode small proteins that lack intrinsic enzymatic activities and they function by binding to cellular regulatory molecules, thereby subverting normal cellular homeostasis. Much effort has focused on identifying protein targets of the E6 and E7 proteins, but it has been estimated that ~98% of the human transcriptome does not encode proteins. There is a growing interest in studying noncoding RNAs as biochemical targets and biological mediators of human papillomavirus (HPV) E6/E7 oncogenic activities. This review focuses on HPV E6/E7 targeting cellular long noncoding RNAs, a class of biologically versatile molecules that regulate almost every known biological process and how this may contribute to viral oncogenesis.
Highlights
Human Papillomaviruses as Oncogenic DriversPapillomaviruses are a large family of non-enveloped viruses with ~8000 base pair, circular, double stranded DNA genomes
E6 and E7 are the only viral genes that are consistently expressed in cancers, and they are necessary for tumor initiation, progression, and maintenance
Consistent with the ability of E7 to cause TP53 stabilization and E6 to target TP53 for degradation, we found that damage-induced noncoding lncRNA (DINO) levels were higher in E7 expressing human foreskin keratinocytes (HFKs) but lower in E6 expressing HFKs than in parental cells [104]
Summary
Papillomaviruses are a large family of non-enveloped viruses with ~8000 base pair, circular, double stranded DNA genomes. They have been detected in almost all vertebrates, are highly host-specific and preferentially infect squamous epithelial tissues. HPV E6 and E7 encode low molecular weight, cysteine-rich, zinc-binding proteins of ~150 and ~100 amino acids, respectively Despite their diminutive size, they are potent oncogenic drivers and are necessary for tumor initiation, progression and maintenance. They are potent oncogenic drivers and are necessary for tumor initiation, progression and maintenance They lack intrinsic enzymatic activities and do not directly bind to specific DNA sequences. RNAs, the long noncoding RNAs (lncRNAs), in the context of HPV-associated carcinogenesis
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