Circular RNA profiling identifies circ102049 as a key regulator of colorectal liver metastasis

CircRNAs play an essential role in the development and progression of various cancers. However, the functions and mechanisms of circRNAs in colorectal liver metastasis have not been fully elucidated. We performed circRNA microarray analysis to screen differentially expressed circRNAs in the pathology of colorectal liver metastasis. QRT-PCR was used to detect the expression of hsa_circ_102049 (circ102049) in colorectal cancer (CRC) samples. CRC cells were transfected with circ102049 overexpression vector or siRNAs to assess the effects of circ102049 in vitro. Bioinformatics analysis, FISH, RIP, RNA pull down and luciferase reporter assays were conducted to confirm the relationship between circ102049, miR-761, miR-192-3p and FRAS1. Moreover, the mechanism by which circ102049 recruited and distributed DGCR8 protein in the cytoplasm was also investigated. We found that circ102049 was highly expressed in primary CRC tumors with liver metastasis, and closely correlated with the prognosis of patients with CRC. Circ102049 significantly enhanced the adhesion, migration and invasion abilities of CRC cells, and promoted CRC progression via a miR-761/miR-192-3p-FRAS1-dependent mechanism. Notably, due to the distribution of DGCR8 protein, circ102049 might also reduce the levels of mature miR-761 and miR-192-3p in the cytoplasm indirectly. In addition, the role of circ102049 in promoting colorectal liver metastasis was also confirmed in vivo. Our findings provide new evidence that circ102049 might be a potential prognostic factor in CRC, and the circ102049-miR-761/miR-192-3p-FRAS1 axis as an anti-metastatic target for CRC patients.