Knockdown of circ_0006225 overcomes resistance to cisplatin and suppresses growth in lung cancer by miR-1236-3p/ANKRD22 axis.

Cisplatin-based chemotherapy is the mainstay of therapeutic agents for lung cancer. Hence, we investigated the role and mechanism of circ_0006225 in tumorigenesis and cisplatin resistance in lung cancer. Levels of circ_0006225, microRNA (miR)-1236-3p and ankyrin repeat domain 22 (ANKRD22) were detected. Cell cisplatin (DDP) sensitivity and growth were determined by Cell Counting Kit-8, cell colony formation, 5-ethynyl-2'-deoxyuridine, and murine xenograft assays, respectively. A high level of circ_0006225 in lung cancer tissues and cells with cisplatin resistance was observed. Circ_0006225 deletion elevated cisplatin sensitivity and constrained proliferation in DDP-resistant lung cancer cells in vitro. Mechanistically, Circ_0006225 was confirmed to modulate ANKRD22 by sequestering miR-1236-3p. Furthermore, the suppressive effects of circ_0006225 downregulation on cisplatin resistance and proliferation in DDP-resistant lung cancer cells were reversed by miR-1236-3p inhibition or ANKRD22 overexpression. Besides that, circ_0006225 silencing also repressed cisplatin resistance and tumor growth in lung cancer in vivo. In conclusion, knockdown of circ_0006225 restrained the growth and reduced cisplatin resistance in lung cancer by the miR-1236-3p/ANKRD22 axis, suggesting a better effective therapeutic target for overcoming cisplatin resistance in lung cancer patients.