Transforming activity of an oncoprotein-encoding circular RNA from human papillomavirus

Abstract

Single-stranded circular RNAs (circRNAs), generated through ‘backsplicing’, occur more extensively than initially anticipated. The possible functions of the vast majority of circRNAs remain unknown. Virus-derived circRNAs have recently been described in gamma-herpesviruses. We report that oncogenic human papillomaviruses (HPVs) generate circRNAs, some of which encompass the E7 oncogene (circE7). HPV16 circE7 is detectable by both inverse RT-PCR and northern blotting of HPV16-transformed cells. CircE7 is N 6 -methyladenosine (m 6 A) modified, preferentially localized to the cytoplasm, associated with polysomes, and translated to produce E7 oncoprotein. Specific disruption of circE7 in CaSki cervical carcinoma cells reduces E7 protein levels and inhibits cancer cell growth both in vitro and in tumor xenografts. CircE7 is present in TCGA RNA-Seq data from HPV-positive cancers and in cell lines with only episomal HPVs. These results provide evidence that virus-derived, protein-encoding circular RNAs are biologically functional and linked to the transforming properties of some HPV.

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• The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs · 2020
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• The Role of microRNAs, Long Non-coding RNAs, and Circular RNAs in Cervical Cancer · 2020
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• Novel insights into the interplay between m6A modification and noncoding RNAs in cancer · 2020
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• Mechanism of RNA modification N6-methyladenosine in human cancer · 2020
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• CircAtlas: an integrated resource of one million highly accurate circular RNAs from 1070 vertebrate transcriptomes · 2020
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• Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1 · 2020
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• Circular RNA circFGFR1 promotes progression and anti-PD-1 resistance by sponging miR-381-3p in non-small cell lung cancer cells · 2019
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