Research progress of circular RNAs in lung cancer

Abstract

Lung cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Despite encouraging results achieved with targeted therapy in recent years, the early diagnosis and treatment of lung cancer remains a major problem. Circular RNA (circRNA), a type of RNA with covalently closed continuous loop structures, has structural stability and certain tissue specificity. Recent studies have found that circRNAs have an important role in tumor development and are expected to be revealed as new targets for tumor prediction and treatment. Research on the biological functions and regulation mechanisms of circRNAs in lung cancer is in its infancy but is gathering momentum. In this review, we discuss the properties, biogenesis, biological function, and research progress of circRNAs in lung cancer to provide a theoretical foundation and new directions for studies on circRNAs in lung cancer.

Keywords: Lung cancer; back-splicing; biogenesis; biomarkers; circular RNA; microRNA sponge; therapeutic target.

Figure 1.

（a）Lariat- driven circularization (exon skipping)：Following canonical splicing, exons in exon-containing lariats undergo back-splicing and circularization, which results in the formation of ecircRNA or EIciRNA molecules. (b) Intron pairing-driven circularization: Flanking long introns containing reverse complementary sequences such as the Alu sequence may promote intron pairing and exon circularization. (c) Resplicing-driven circularization：mature mRNA exons may form EcircRNAs by back-splicing and circularization (d) Following canonical splicing, introns may form lariats to escape the usual intron debranching and degradation. Then ciRNAs are formed. (e) CircRNAs function as miRNA sponges. This figure is adapted from Wang et al.^18.