circ-ACACA promotes proliferation, invasion, migration and glycolysis of cervical cancer cells by targeting the miR-582-5p/ERO1A signaling axis

Abstract

Circular RNAs (circ) have been reported to serve crucial roles in the regulation of cancer occurrence and devel- opment. The present study aimed to investigate the role of circ-acetyl-CoA carboxylase α (ACACA) in the progression of cervical cancer (CC). The expression levels of circ-ACACA in several CC cell lines were first determined using reverse transcription-quantitative PCR. circ-ACACA expression was subsequently knocked down to evaluate its effects on the viability, proliferation, apoptosis, invasion and migration of CC cells using MTT, colony formation, TUNEL, transwell and wound healing assays, respectively. 13C-labeling of intracellular metabolites and analysis of glucose consump- tion and lactate production were performed to determine the levels of glycolysis. In addition, the expression levels of endoplasmic reticulum oxidoreductase 1α (ERO1α; ERO1A) and glycolysis-related proteins were analyzed using western blotting. The binding interactions among circ-ACACA, microRNA (miR)-582-5p and ERO1A were validated using dual-luciferase reporter assays. Subsequently, rescue experi- ments were performed to determine the potential underlying mechanism by which circ-ACACA affected CC cell functions. The results revealed that circ-ACACA expression was signifi- cantly upregulated in CC cells and silencing of circ-ACACA significantly reduced the proliferation, invasion and migra- tion, and promoted the apoptosis of CC cells. Knockdown of circ-ACACA markedly inhibited glycolysis in CC cells. However, the effects of silencing of circ-ACACA on CC cells were reversed following transfection with the miR-582-5p inhibitor or pcDNA3.1-ERO1A overexpression plasmid. In conclusion, to the best of our knowledge, the present study was the first to investigate the role of circ-ACACA in CC progression. The results suggested that circ-ACACA may promote CC tumorigenesis and glycolysis by targeting the miR-582-5p/ERO1A signaling axis. Therefore, circ-ACACA may be a promising biomarker for CC diagnosis and treatment.