Circ_0029803 serves as the sponge of miR-216b-5p to promote the progression of colorectal cancer by regulating SKIL expression

Abstract

Abstract Background Circular RNA 0029803 (circ_0029803) was found to be upregulated in colorectal cancer (CRC) tissues, but its function and underlying molecular mechanism are not studied in CRC. Methods The expression levels of circ_0029803, microRNA-216b-5p (miR-216b-5p), and ski-oncogene-like (SKIL) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to affirm the existence of circ_0029803. Cell proliferation, apoptosis, migration, and invasion were assessed by colony formation, flow cytometry, and Transwell assays, respectively. A glucose and lactate assay kit was used to detect glucose consumption and lactate production. Western blot was applied to analyze the levels of all proteins. Dual-luciferase reporter assay was performed to assess the relationship between miR-216b-5p and circ_0029803 or SKIL. Tumor xenograft models were established to elucidate the effect of circ_0029803 in vivo. Results Circ_0029803 expression was enhanced in CRC tissues and cells, and the 5-year overall survival rate of patients with high circ_0029803 expression was substantially reduced. Circ_0029803 depletion retarded proliferation, migration, invasion, EMT and glycolysis of CRC cells in vitro as well as the tumor growth in vivo. Mechanically, circ_0029803 could serve as miR-216b-5p sponge to regulate its expression, and miR-216b-5p knockdown reversed the inhibition of si-circ_0029803 on the malignant behaviors of CRC cells. Additionally, as the target mRNA of miR-216b-5p, SKIL could counteract the inhibitory effect of miR-216b-5p on the development of CRC cells. Importantly, silencing circ_0029803 reduced SKIL expression via sponging miR-216b-5p. Conclusion Circ_0029803 knockdown hindered proliferation, migration, invasion, EMT, and glycolysis and promoted apoptosis in CRC cells by modulating the miR-216b-5p/SKIL axis.