Intergenic CircRNA <i>Circ_0007379</i> Inhibits Colorectal Cancer Progression by Modulating <i>miR-320a</i> Biogenesis in a KSRP-Dependent Manner

Abstract

Circular RNAs (circRNAs) are covalently closed RNA structures that play multiple roles in tumorigenesis and progression. Compared with exon‒intron circRNAs, the biological functions and implications of intergenic circRNAs in human cancer are still poorly understood. Here, we performed circRNA microarray analysis and identified an intergenic circRNA, <i>circ_0007379</i>, that was significantly downregulated in patients with colorectal cancer (CRC). The biogenesis of <i>circ_0007379</i> was mediated by reverse complementary matches (RCMs) and was negatively regulated by the RNA helicase DHX9. Functionally, <i>circ_0007379</i> suppressed CRC cell growth and metastasis in cell culture as well as in patient-derived organoid and xenograft models. Mechanistically, <i>circ_0007379</i> acted as a scaffold to facilitate the processing of both <i>pri-miR-320a</i> and <i>pre-miR-320a</i> in a KSRP-dependent manner, leading to <i>miR-320a</i> maturation and subsequent repression of transcription factor RUNX1 expression. Thus, our findings establish a previously unrecognized function of circRNA in inhibiting CRC progression.