Circ_0030998 Promotes Tumor Proliferation and Angiogenesis by Sponging miR-567 to Regulate VEGFA in Colorectal Cancer

Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Accumulating studies have demonstrated that circular RNAs (circRNAs), a novel class of noncoding RNAs, are involved in pathological processes, especially in the development of cancers. But the roles of circRNAs in CRC are largely unknown.MethodsThe microarray data GSE138589 was analyzed and qRT-PCR was performed to screen out the circRNA with the highest upregulated level in CRC. QRT-PCR was used to determine the expression of genes in different tissues or cells. RNA-FISH was conducted to identify the subcellular localization of Circ_0030998. In vitro and in vivo assays were performed to determine the effect of Circ_0030998 on the CRC cells proliferation and angiogenesis. The relationships of Circ_0030998, miR-567 and VEGFA were predicted and validated using bioinformatic tools, RIP and luciferase assays.ResultsWe identified a novel circRNA, Circ_0030998, was upregulated in CRC tissues and cells, and its upregulation was related with poor prognosis in CRC patients. Circ_0030998 promoted CRC cells proliferation and angiogenesis. RNA-FISH showed that Circ_0030998 was mainly localized in the cytoplasm of CRC cells. Mechanistic studies demonstrated that Circ_0030998 acted as a miR-567 sponge to relieve its inhibitory effect on VEGFA. Rescue assays validated that Circ_0030998 functioned in CRC cells proliferation and angiogenesis relying on VEGFA.ConclusionsThe present study clarified the Circ_0030998/miR-567/VEGFA regulation axis and indicated that Circ_0030998 could be a potential therapeutic target for CRC.