Department of Cardiothorcic Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China.
J Biochem Mol Toxicol. 2024 Nov;38(11):e23830. doi: 10.1002/jbt.23830.
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.
基于顺铂的化疗是肺癌治疗药物的主要手段。因此，我们研究了 circ_0006225 在肺癌发生和顺铂耐药中的作用和机制。检测 circ_0006225、microRNA（miR）-1236-3p 和锚蛋白重复域 22（ANKRD22）的水平。通过细胞计数试剂盒-8、细胞集落形成、5-乙炔基-2'-脱氧尿苷和小鼠异种移植实验分别测定细胞顺铂（DDP）敏感性和生长。观察到肺癌组织和耐顺铂的细胞中 circ_0006225 水平较高。circ_0006225 缺失可提高体外耐顺铂肺癌细胞的顺铂敏感性和增殖能力。机制上，circ_0006225 通过结合 miR-1236-3p 来调节 ANKRD22。此外，通过抑制 miR-1236-3p 或过表达 ANKRD22，可逆转 circ_0006225 下调对耐顺铂肺癌细胞中顺铂耐药和增殖的抑制作用。此外，circ_0006225 沉默也抑制了肺癌体内的顺铂耐药和肿瘤生长。总之，circ_0006225 的敲低通过 miR-1236-3p/ANKRD22 轴抑制肺癌的生长并降低顺铂耐药性，为克服肺癌患者的顺铂耐药提供了更好的有效治疗靶点。
