CircCDC6 restrains tumor growth and glycolysis energy metabolism in colorectal cancer via regulating miR-3187-3p and downstream PRKAA2.

Abstract

The aberrant downregulation of circCDC6 in colorectal cancer (CRC) was previously identified by circRNA microarray analysis. However, the detailed role of circCDC6 in CRC is still lacking. We thus investigated the function of circCDC6 in CRC. The expression of circCDC6, miR-3187-3p and PRKAA2 mRNA was checked by real-time quantitative PCR (RT-qPCR). Cell growth was evaluated by MTT, EdU and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Glycolysis was evaluated by glycolysis stress test and lactic acid level. The expression of PRKAA2, HK2 and LDHA proteins was checked by western blotting. The potential binding between miR-3187-3p and circCDC6 or PRKAA2 was confirmed by dual-luciferase reporter assay, RIP assay and pull-down assay. Xenograft model was established in nude mice. CircCDC6 showed poor expression in CRC tumor samples and cells. CircCDC6 ectopic expression repressed CRC cell proliferation, survival and glycolysis energy metabolism. MiR-3187-3p was targeted by circCDC6, and miR-3187-3p depletion also repressed CRC cell growth and glycolysis. PRKAA2 was a downstream target of circCDC6/miR-3187-3p pathway, and circCDC6 upregulated PRKAA2 expression via targeting miR-3187-3p. PRKAA2 knockdown rescued the functional effects of circCDC6 ectopic expression. CircCDC6 overexpression in vivo impeded tumor development in animal models. CircCDC6, acting as a tumor inhibitor, repressed tumor growth and glycolysis metabolism in CRC via targeting the miR-3187-3p/PRKAA2 axis, which partly clarified the role of circCDC6 in CRC.