circMTO1 sponges microRNA-219a-5p to enhance gallbladder cancer progression via the TGF-β/Smad and EGFR pathways

Circular mitochondrial translation optimization 1 homologue (circMTO1) has been reported to regulate the tumorigenesis of different types of cancer; however, the role of circMTO1 in gallbladder cancer (GBC) remains unknown. The present study aimed to identify the potential miRNAs and target genes of circMTO1 during GBC progression, and clarify the regulatory mechanism between circMTO1 and miRNAs or target genes. The present study performed MTT and Transwell assays, and Annexin V staining to assess cell viability, migration and apoptosis, respectively. In addition, a lymphatic vessel formation assay was performed to assess tube formation of human dermal lymphatic endothelial cells (HDLECs), and GBC-SD and NOZ cells. The results demonstrated that circMTO1 knockdown significantly attenuated the viability and migration of GBC cells and tube formation of HDLECs, and promoted apoptosis, indicating a tumor-promoting role of circMTO1. In addition, transfection with microRNA (miRNA/miR)-219a-5p inhibitor rescued short hairpin RNA-circMTO1-inhibited tumorigenesis of GBC cells, suggesting that miR-219a-5p acts as a downstream effector for circMTO1. Mechanistically, transfection with miR-219a-5p mimic suppressed the expression levels of Smad2/4 and epidermal growth factor receptor. Analysis of The Cancer Genome Atlas datasets revealed that circMTO1 expression was associated with overall survival and the stage of patients with GBC. Taken together, the results of the present study provide novel insight for the role of circMTO1-induced GBC tumorigenesis via regulation of miR-219a-5p expression.