Circular RNA circ_ASAP2 regulates drug sensitivity and functional behaviors of cisplatin-resistant gastric cancer cells by the miR-330-3p/NT5E axis.

This study aims to explore the biological actions of circular RNA (circRNA) ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 (circ_ASAP2, circ_0006089) in cisplatin (DDP) resistance of gastric cancer. Circ_ASAP2, ecto-5'-nucleotidase (NT5E) and miR-330-3p were quantified by quantitative real-time PCR or western blot. The measurements of the IC50 value and cell proliferation were done using 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell colony formation, cell cycle distribution, apoptosis, migration and invasion were evaluated by the colony formation, flow cytometry and transwell assays. Dual-luciferase reporter assay was performed to confirm the targeted relationship between different molecules. The role of circ_ASAP2 in tumor growth was gauged by in vivo animal studies. Circ_ASAP2 and NT5E were overexpressed in DDP-resistant gastric cancer tissues and cells. Knockdown of circ_ASAP2 promoted DDP sensitivity, apoptosis and repressed proliferation, migration and invasion of DDP-resistant gastric cancer cells in vitro and diminished tumor growth in vivo. Moreover, NT5E was a downstream effector of circ_ASAP2 in regulating cell DDP sensitivity and functional behaviors. Mechanistically, circ_ASAP2 directly bound to miR-330-3p to promote NT5E expression. Furthermore, circ_ASAP2 modulated cell DDP sensitivity and functional behaviors by targeting miR-330-3p. Knockdown of circ_ASAP2 promoted DDP sensitivity and suppressed malignant behaviors of DDP-resistant gastric cancer cells through targeting the miR-330-3p/NT5E axis.