Abstract
Circular RNAs (circRNAs), a class of covalently closed RNAs formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in RH4, a representative cell line of alveolar rhabdomyosarcoma. We demonstrated that circVAMP3 has a differential m6A pattern opposed to its linear counterpart, suggesting that the two isoforms can be differently regulated by such RNA modification. Moreover, we show how circVAMP3 depletion in alveolar rhabdomyosarcoma cells can impair cell cycle progression, through the alteration of the AKT-related pathways, pointing to this non-coding RNA as a novel regulator of the alveolar rhabdomyosarcoma progression and as a putative future therapeutic target.
Highlights
IntroductionCircular RNAs (circRNAs) are covalently closed single-stranded RNA molecules originated from a particular splicing event, called back-splicing, in which a 5’ splice site of a precursor molecule is joined to an upstream 3’ splice site, producing the circularization of the intervening exons [1,2].In recent years, circRNAs have stepped up as a large class of eukaryotic transcripts, often conserved among different species and whose expression is modulated during physiological and pathological processes [1,2,3,4,5].CircRNAs regulate gene expression at different levels: they can act as miRNA sponges [1,6,7], as protein scaffolds [8,9], as templates for cap-independent translation [10,11,12] and as regulators of parental gene transcription [13].CircRNA functions and the modulation of their expression have been studied in a variety of cellular processes, such as proliferation, differentiation, metabolic reprogramming, cancer onset and progression [14,15,16]
Vesicle-Associated Membrane Protein 3 (VAMP3) is a gene able to generate a protein belonging to the vesicle-associated membrane protein (VAMP)/synaptobrevin family
From the analysis of RNA-sequencing data produced in our laboratory (GEO: GSE117609) [24], we detected both the circular and linear VAMP3 isoforms in human primary myoblasts, embryonal rhabdomyosarcoma (ERMS) RD cells and alveolar rhabdomyosarcoma (ARMS) RH4 cells
Summary
Circular RNAs (circRNAs) are covalently closed single-stranded RNA molecules originated from a particular splicing event, called back-splicing, in which a 5’ splice site of a precursor molecule is joined to an upstream 3’ splice site, producing the circularization of the intervening exons [1,2].In recent years, circRNAs have stepped up as a large class of eukaryotic transcripts, often conserved among different species and whose expression is modulated during physiological and pathological processes [1,2,3,4,5].CircRNAs regulate gene expression at different levels: they can act as miRNA sponges [1,6,7], as protein scaffolds [8,9], as templates for cap-independent translation [10,11,12] and as regulators of parental gene transcription [13].CircRNA functions and the modulation of their expression have been studied in a variety of cellular processes, such as proliferation, differentiation, metabolic reprogramming, cancer onset and progression [14,15,16]. CircRNAs have stepped up as a large class of eukaryotic transcripts, often conserved among different species and whose expression is modulated during physiological and pathological processes [1,2,3,4,5]. CircRNAs regulate gene expression at different levels: they can act as miRNA sponges [1,6,7], as protein scaffolds [8,9], as templates for cap-independent translation [10,11,12] and as regulators of parental gene transcription [13]. CircRNA functions and the modulation of their expression have been studied in a variety of cellular processes, such as proliferation, differentiation, metabolic reprogramming, cancer onset and progression [14,15,16].
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