Abstract
Circular RNA (circRNA) is a covalently closed RNA structure that has several proposed functions related to cancer development. Recently, cancer-specific and tissue-specific circRNAs have been identified by high-throughput sequencing and are curated in publicly available databases. CircRNAs have features that are ideal properties of biomarkers, including conservation, abundance, and stability in plasma, saliva, and urine. Many circRNAs with predictive and prognostic significance in cancer have been described, and functional mechanisms for some circRNAs have been suggested. CircRNA also has great potential as a noninvasive biomarker for early cancer detection, although further investigation is necessary before clinical application is feasible.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."
Highlights
RNA molecules with a circular structure were first reported in plant viroids in 1976 [1] and in eukaryotic cells in 1979 [2]
Alternative strategies are necessary to identify circular RNA (circRNA) to compensate for inability to enrich polyadenylated transcripts [49]
CircRNA has emerged as an intriguing multifaceted cancer biomarker
Summary
RNA molecules with a circular structure were first reported in plant viroids in 1976 [1] and in eukaryotic cells in 1979 [2]. Multiple circRNAs have been reported with oncogenic and tumor-suppressive potential [17]. The second mechanism involves RNA-binding proteins (RBP) attaching to flanking introns, stabilizing intron pairs to promote circularization [28, 29]. Multiple potential biological functions for circRNA have been proposed (Fig. 2). Some circRNAs contain an open-reading frame (ORF) and have an internal ribosomal entry site (IRES) to mediate translation and compensate for lack of 50 cap and 30 end [43, 44]. CircRNA can help form scaffolds to stabilize protein complexes, including those involving RBPs. C, Function as template for translation. Some nuclear localized circRNAs can promote parental gene transcription [31]
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