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

Abstract 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.