Mechanisms Regulating Abnormal Circular RNA Biogenesis in Cancer

SIMPLE SUMMARY: Circular RNAs (circRNAs) are circular RNA molecules without a 5′ cap and a 3′ poly(A) tail structure, which play an important role in tumor development, invasion and metastasis, etc. However, the mechanism of circRNA dysregulation in cancer remains unclear. Different from the classic splicing of linear RNA, circRNA is formed by back-splicing and is regulated by many cis-acting elements and trans-acting proteins. Exploring how the dysregulation of cis-regulatory elements and trans-acting proteins in tumor cells affects the biogenesis of circRNA, which in turn affects the development and prognosis of cancer, is of great significance for circRNA to become a cancer biomarker and therapeutic target. ABSTRACT: Circular RNAs (circRNAs), which are a class of endogenous RNA with covalently closed loops, play important roles in epigenetic regulation of gene expression at both the transcriptional and post-transcriptional level. Accumulating evidence demonstrated that numerous circRNAs were abnormally expressed in tumors and their dysregulation was involved in the tumorigenesis and metastasis of cancer. Although the functional mechanisms of many circRNAs have been revealed, how circRNAs are dysregulated in cancer remains elusive. CircRNAs are generated by a “back-splicing” process, which is regulated by different cis-regulatory elements and trans-acting proteins. Therefore, how these cis and trans elements change during tumorigenesis and how they regulate the biogenesis of circRNAs in cancer are two questions that interest us. In this review, we summarized the pathways for the biogenesis of circRNAs; and then illustrated how circRNAs dysregulated in cancer by discussing the changes of cis-regulatory elements and trans-acting proteins that related to circRNA splicing and maturation in cancer.