Circ_101692 promotes the proliferation, invasion and glycolysis of colorectal cancer through the regulation of miR-449b-5p/GOLPH3 axis

BackgroundColorectal cancer (CRC) is one of the most common malignancies worldwide and a major threat to human life and health. Circular RNA (circRNA)-microRNA (miRNA)-mRNA mechanism is considered to occur in various cancers. However, the mechanism of circ_101692 in CRC is still unclear.MethodsQuantitative real-time PCR was used to detect the expression of circ_101692, miR-449b-5p and Golgi phosphoprotein 3 (GOLPH3) in CRC tissues and cell lines. Cell proliferation was determined using cell counting kit-8 (CCK8), colony formation assay and 5-ethynyl-2 '-deoxyuridine (EdU). Flow cytometry and transwell were performed to measure apoptosis and cell invasion, respectively. Besides, glucose uptake and lactate production were tested using commercial kits to determine the glycolytic of CRC. Furthermore, dual-luciferase reporter assay and RNA immunoprecipitation assay were employed to verify the relationship between miR-449b-5p and circ_101692 or GOLPH3. And the protein levels were monitored using western blot assay. The xenotransplantation model was established to study the role of circ_101692 in vivo.ResultsCirc_101692 and GOLPH3 were highly expressed, while miR-449b-5p expression was down-regulated in CRC tissues and cell lines compared to normal tissues and cell lines. Circ_101692 negatively targeted miR-449b-5p, and GOLPH3 was the downstream gene of miR-449b-5p. Silencing circ_101692 suppressed CRC cell proliferation, invasion and glycolysis, as well as promoted apoptosis, while these influences could be reverted by miR-449b-5p inhibitor. Similarly, overexpression of GOLPH3 abolished the influence of miR-449b-5p mimic on CRC cell behavior. In addition, silencing of circ_101692 restricted CRC tumor growth in vivo.ConclusionOur results showed that circ_101692 promoted CRC progression by modulating the miR-449b-5p/GOLPH3 axis, implying that circ_101692 might be a possible target for CRC treatment.