circRNA circ-ZEB1 promotes gallbladder carcinomas progression by regulating the miR-144-3p/ZEB2 axis.

Abstract

Gallbladder cancer (GBC) is the most common and aggressive type of tumor occurring in the biliary system. Several studies have indicated the possible functions of circular RNAs (circRNAs) in GBC tumorigenesis. This research aimed to explore the roles of a novel circRNA, circ-ZEB1 (hsa_circ_0093509), in GBC. The expressions of circ-ZEB1, miR-144-3p, and ZEB2 in GBC cells were detected using RT-qPCR or western blot. The subcellular localization of circ-ZEB1 in GBC cells was determined. The function of circ-ZEB1, miR-144-3p, and ZEB2 in GBC cells was assessed by using CCK-8, EdU staining, colony formation, or Transwell assays. The relationship among miR-144-3p and corresponding targets, circ-ZEB1 and ZEB2, was confirmed. Additionally, xenograft experiments were conducted to assess the role of circ-ZEB1 in tumor growth in vivo. circ-ZEB1 was predominantly found in the cytoplasmic region of GBC cells and was upregulated in the GBC cell lines. Suppression of circ-ZEB1 reduced the proliferation and migration of GBC-SD and SGC-996 cells. Knockdown of circ-ZEB1 attenuates tumor growth in vivo. Mechanistically, circ-ZEB1 sponged miR-144-3p, which targeted ZEB2. Additionally, inhibition of miR-144-3p rescues the effects of circ-ZEB1 or ZEB2 knockdown. These results clarified a vital role of the circ-ZEB1/miR-144-3p/ZEB2 axis in GBC advancement, and may serve as a novel therapeutic target for GBC treatment.