The important regulatory roles of circRNA-encoded proteins or peptides in cancer pathogenesis (Review)

Abstract

Circular RNAs (circRNAs) represent a class of RNA molecules characterized by their covalently closed structures. There are three types of circRNAs, namely exonic circRNAs, exon-intron circRNAs and circular intronic RNAs. To date, four distinct mechanisms have been unveiled through which circRNAs exert their functional influence, including serving as microRNA (miRNA) sponges, interacting with RNA binding proteins (RBPs), modulating parental gene transcription and acting as templates for translation. Of note, among these mechanisms, the miRNA/RBP sponge function has been the most investigated one. Recent research has uncovered the presence of various proteins or peptides encoded by circRNA. CircRNAs are translated independent of the 5′ cap and 3′ polyA tail, which are typical elements for linear RNA translation. Some unique elements, such as internal ribosome entry sites and N-methyladenosine modifications, facilitate the initiation of translation. These circRNA-encoded proteins or peptides participate in diverse signalling pathways and act as important regulators in carcinogenesis by influencing cell proliferation, migration, apoptosis and other key processes. Consequently, circRNA-encoded proteins or peptides have great potential as therapeutic targets for anticancer drugs. The present comprehensive review aimed to systematically summarize the current understanding of circRNA-encoded proteins or peptides and to unveil their roles in carcinogenesis.