环状 RNA ZKSCAN1 通过 miR-185-5p/TAGLN2 轴促进肺腺癌进展。
CircRNA ZKSCAN1 promotes lung adenocarcinoma progression by miR-185-5p/TAGLN2 axis.
机构信息
Department of Thoracic Surgery, Zigong Third People's Hospital, Zigong, China.
出版信息
Thorac Cancer. 2023 Jun;14(16):1467-1476. doi: 10.1111/1759-7714.14889. Epub 2023 Apr 27.
BACKGROUND
Circ-ZKSCAN1 has been found to accelerate non-small cell lung cancer (NSCLC) progression; however, the role and mechanism of circ-ZKSCAN1 in lung adenocarcinoma (LUAD) cisplatin (DDP) resistance remain unclear.
METHODS
Levels of genes and proteins were examined using qRT-PCR. Functional experiments were performed using CCK-8 assay, flow cytometry, transwell assay and xenograft model assay, respectively. Glucose metabolism was calculated by detecting glucose consumption, lactate production, ATP and HK-2 levels. The interaction between miR-185-5p and circ-ZKSCAN1 or transgelin 2 (TAGLN2) was validated by dual-luciferase reporter assay.
RESULTS
Circ-ZKSCAN1 was highly expressed in DDP-resistant LUAD tissues and cell lines, and circ-ZKSCAN1 knockdown weakened DDP resistance and suppressed cell viability, migration, invasion, and glycolysis in LUAD. Circ-ZKSCAN1 acted as a sponge of miR-185-5p, and the regulatory effects of circ-ZKSCAN1 knockdown on LUAD were reversed by miR-185-5p downregulation. Meanwhile, miR-185-5p directly targeted TAGLN2, and performed anticancer effects by regulating TAGLN2. Importantly, silencing of circ-ZKSCAN1 hindered tumor growth and promoted DDP sensitivity in vivo via regulating miR-185-5p and TAGLN2.
CONCLUSION
Circ-ZKSCAN1 promoted LUAD tumorigenesis and DDP resistance by regulating miR-185-5p/TAGLN2 axis.
背景
Circ-ZKSCAN1 已被发现可加速非小细胞肺癌（NSCLC）的进展；然而，circ-ZKSCAN1 在肺腺癌（LUAD）顺铂（DDP）耐药中的作用和机制仍不清楚。
方法
使用 qRT-PCR 检测基因和蛋白水平。分别通过 CCK-8 assay、流式细胞术、transwell assay 和异种移植模型 assay 进行功能实验。通过检测葡萄糖消耗、乳酸生成、ATP 和 HK-2 水平来计算葡萄糖代谢。通过双荧光素酶报告实验验证 miR-185-5p 与 circ-ZKSCAN1 或转凝胶蛋白 2（TAGLN2）之间的相互作用。
结果
circ-ZKSCAN1 在 DDP 耐药 LUAD 组织和细胞系中高表达，circ-ZKSCAN1 敲低减弱了 LUAD 的 DDP 耐药性，并抑制了 LUAD 细胞活力、迁移、侵袭和糖酵解。circ-ZKSCAN1 作为 miR-185-5p 的海绵，miR-185-5p 下调逆转了 circ-ZKSCAN1 敲低对 LUAD 的调控作用。同时，miR-185-5p 直接靶向 TAGLN2，并通过调节 TAGLN2 发挥抗癌作用。重要的是，沉默 circ-ZKSCAN1 通过调节 miR-185-5p 和 TAGLN2 抑制体内肿瘤生长并提高 DDP 敏感性。
结论
circ-ZKSCAN1 通过调节 miR-185-5p/TAGLN2 轴促进 LUAD 肿瘤发生和 DDP 耐药。
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