ISSN : 2146-3123
E-ISSN : 2146-3131

Hypoxia-induced Circular RNA hsa_circ_0006508 Promotes the Warburg Effect in Colorectal Cancer Cells
Yugang Xu1, Ying Zhang2, Wenli Hao1, Wen Zhao3, Guang Yang1, Changqing Jing4
1Department of General Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Qingdao, China
2Department of Hepatobiliary Surgery, The Affiliated Taian City Central Hospital of Qingdao University, Taian, China
3Department of General Surgery, The Second People’s Hospital of Daiyue District, Taian, China
4Department of General Surgery, Shandong Provincial Hospital, Shandong, China
DOI : 10.4274/balkanmedj.galenos.2022.2022-7-80

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.

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