The emerging role of circular RNAs in breast cancer

Abstract

Breast cancer (BCa) is one of the most frequently diagnosed cancers and leading cause of cancer deaths among females worldwide. Circular RNAs (circRNAs) are a new class of endogenous regulatory RNAs characterized by circular shape resulting from covalently closed continuous loops that are capable of regulating gene expression at transcription or post-transcription levels. With the unique structures, circRNAs are resistant to exonuclease RNase R and maintain stability more easily than linear RNAs. Recently, an increasing number of circRNAs are discovered and reported to show different expression in BCa and these dysregulated circRNAs were correlated with patients' clinical characteristics and grade in the progression of BCa. CircRNAs participate in the bioprocesses of carcinogenesis of BCa, including cell proliferation, apoptosis, cell cycle, tumorigenesis, vascularization, cell invasion, migration as well as metastasis. Here we concentrated on biogenesis and function of circRNAs, summarized their implications in BCa and discussed their potential as diagnostic and therapeutic targets for BCa.

Keywords: Breast cancer (BCa); biomarker; circRNA; miRNA sponge.

Figure 1. Schematic representation of circRNA splicing process

(A) CircRNAs are ubiquitous in eukaryotic cells and mostly transcribed from protein-coding genes by RNA polymerase II. (B) Linear mRNA is generated through conventional splicing pattern. (C) Exonic circRNA is formed through a shearing process called ‘head-to-tail’ or ‘backsplicing’. (D) Another kind of circRNA named ciRNA whose lose loop structure is produced from lariat intron’s failure to debranch at the branch point site. (E) Some of the EcircRNAs contain multiple quantities of exons, making up a high proportion of circRNAs. (F) Circularization of EIciRNAs occurs in a form of retaining introns between exons. (G) Complicated AS event contributes to the occurrence of ES event.

Figure 2. The biological function of circRNAs

(A) CircRNAs can function as miRNA sponge to compete endogenous RNA and sequester miRNAs from binding mRNA targets to influence downstream protein translation. (B) CiRNAs and ElciRNAs can bind to RNA polymerase II, and then interact with U1 snRNP and promote transcription of their parental genes. (C) CircRNAs can also act as RBP sponge to interact with RBPs, forming RNA–protein complex (RPC) to function in the assembly of RBP factories or their allosteric regulators. (D) Some circRNAs which contains the IRES could have translation potential.