Circular RNA pappalysin-1 enhances glycolysis via microRNA-656-3p targeting G-protein subunit gamma-5 to promote colon cancer progression

Colon Cancer (CC) is a common malignant tumor. The aim of this study was to investigate the role and regulatory mechanism of circular RNA pappalysin-1 (circ-PAPPA; hsa_circ_0088233) in CC. In cancer tissues from CC patients, circ-PAPPA expression was measured and its relationship with patients’ clinical features was analyzed. Plasmid vectors or oligonucleotides interfering with the expression of circ-PAPPA, microRNA (miR)-656–3p or G-protein subunit Gamma-5 (GNG5) were transfected into CC cells. Cell viability was detected by MTT and colony formation assay; apoptosis was detected by flow cytometry; and cell migration and invasion were detected by wound healing assay and Transwell. Glycolytic capacity of CC cells was assessed by measuring glucose uptake and lactate production using commercial kits. The targeting relationship between miR-656–3p and circ-PAPPA or GNG5 was verified by bioinformatics website starBase and dual luciferase reporter gene assay assays. Circ-PAPPA was upregulated in CC and was negatively correlated with benign pathological features and 5-year survival rates of CC patients. Circ-PAPPA silencing inhibited the growth and glycolysis of CC cells through upregulating miR-656–3p. GNG5, a target of miR-656–3p, could reverse the impacts of silencing circ-PAPPA on CC cells. Circ-PAPPA may play an oncogenic role in CC by promoting cell growth and glycolysis through the miR-656–3p/GNG5 axis.