Hypoxia-induced Circular RNA hsa_circ_0006508 Promotes the Warburg Effect in Colorectal Cancer Cells

Abstract

Background: The hypoxia-induced Warburg effect promotes colorectal cancer malignancy with altered circular RNA (circRNA) expression. Aims: To investigate the association with the Warburg effect in colorectal cancer and whether has_circ_0006508 can be induced by hypoxia. Study design: In vitro cell lines and human-sample study. Methods: The biological functions of circ_0006508 and miR-1272 in the viability, colony formation, and glycolysis under hypoxic conditions were determined by loss-of-function and gain-of-function experiments. The chromatin immunoprecipitation assay was used to demonstrate the direct binding between circ_0006508 promoters and hypoxia-inducible factor 1α (HIF-1α). Transcription activity was subjected to the Luciferase reporter assay. The correlation of circ_0006508 and miR-1272 with overall survival was determined with the Kaplan-Meier analysis. Results: Upregulated circ_0006508 and downregulated miR-1272 were observed in colorectal cancer samples, which was associated with the TNM stage and overall survival. Functional assays demonstrated that the hypoxia-induced upregulated circ_0006508 and downregulated miR-1272 promoted the viability and Warburg effect of colorectal cancer in vitro. Mechanistically, HIF-1α-induced circ_0006508 could directly sponge miR-1272, which played a suppressive role in glycolysis. Conclusion: Circ_0006508-mediated miR-1272 inhibition could promote the malignant behaviors of colorectal cancer with an upregulated Warburg effect.