Abstract
Background
Colorectal cancer (CRC) is highly prone to metastasis, leading to a continual increase in the number of deaths each year. One of the commonly used clinical treatments for CRC metastasis is anti-angiogenesis, and vasculogenic mimicry (VM) is considered to be one of the important reasons for the unsatisfactory effect of anti-vascular therapy. Circular RNA (CircRNA) may have an essential regulatory effect during the development of VM and appears to be an ideal marker for fluid biopsy. Therefore, exploring the role of circular RNA in the formation of VM is of great value to the diagnosis and treatment of CRC.
Methods
The differentially expressed circRNAs in CRC were obtained by full transcriptome sequencing. Then the back splice site and its good stability were verified by Sanger sequencing, RNase R and Actinomycin D experiments. Then, the effects of Circ4207 on the growth, invasion and VM of CRC were investigated in vitro and in vivo. The regulatory mechanism between Circ4207 and miR-20b-5p/VEGFA was further confirmed by bioinformatics, fluorescence in situ hybridization (FISH) and dual luciferase reporting experiments. Finally, the serum levels of Circ4207 in patients with colorectal cancer were detected to evaluate its clinical diagnostic value.
Results
Circ4207 is highly expressed in CRC. Circ407 promotes the proliferation and invasion of colorectal cancer and also facilitates the formation of vascular mimicry. Further studies revealed that Circ4207 primarily enhances the formation of vasculogenic mimicry through the miR-20b-5p/VEGFA axis. The study found higher levels of Circ4207 in the serum of patients with colorectal cancer (P < 0.001).
Conclusions
Circ4207 promotes the formation of vasculogenic mimicry in colorectal cancer through the miR-20b-5p/VEGFA axis. It is suggested that it can be used as a potential liquid biopsy marker and a novel therapeutic target for CRC.