Intergenic CircRNA Circ_0007379 Inhibits Colorectal Cancer Progression by Modulating miR-320a 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, circ_0007379 , that was significantly downregulated in patients with colorectal cancer (CRC). The biogenesis of circ_0007379 was mediated by reverse complementary matches (RCMs) and was negatively regulated by the RNA helicase DHX9. Functionally, circ_0007379 suppressed CRC cell growth and metastasis in cell culture as well as in patient-derived organoid and xenograft models. Mechanistically, circ_0007379 acted as a scaffold to facilitate the processing of both pri-miR-320a and pre-miR-320a in a KSRP-dependent manner, leading to miR-320a maturation and subsequent repression of transcription factor RUNX1 expression. Thus, our findings establish a previously unrecognized function of circRNA in inhibiting CRC progression.

CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis

“…CircRNAs can act as oncogenes or tumor suppressor genes and are strongly linked to the development and metastasis of BC 4 , 5 , 6 , 7 and other types of tumors. 8 , 9 , 10 CircRNAs can act by sponging microRNAs (miRNAs), 11 encoding proteins, 12 , 13 and regulating parental genes. 14 , 15 , 16 CircZCCHC2, a 374 bp-long-circRNA derived from exons 2–5 of the ZCCHC2 transcript (chr18: 60206913–60217693), has previously been reported to be associated with hepatocellular carcinoma, 17 while its potential role in BC has not been investigated to date.…”

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice

“…However, the precise mechanism behind this phenomenon has not been elucidated in their study. A recent study proposed that circRNA could promote the processing and mature of miRNA by acting as a scaffold [ 30 ]. In this study, actinomycin D treatment validates that circAKT3 enhances the stability of miR-106a-5p.…”

Exploring the Multifaceted Biologically Relevant Roles of circRNAs: From Regulation, Translation to Biomarkers

“…Their higher stability and multiple biological roles in regulating different pathways have made them attractive candidates for applications as biomarkers and for the study of potential regulatory functions in various biological contexts. Thus far, circRNAs have been revealed to play biologically significant roles in regulating tumorigenesis and metastasis in different types of cancer [37][38][39][40][41], brain development and diseases [42][43][44], bone development and diseases [45][46][47][48], myogenesis and myopathies [49,50], aging [51], and many other diseases and biological processes [52][53][54][55][56][57][58]. Another arena in which circRNAs have recently garnered tremendous levels of functional importance is the regulation of cardiovascular development and diseases [59][60][61][62][63][64].…”