The Second Internal Medicine Department, Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan, China.
J Clin Lab Anal. 2022 May;36(5):e24408. doi: 10.1002/jcla.24408. Epub 2022 Apr 8.
Circular RNAs (circRNAs) serve as critical regulators in the chemoresistance of human cancers, including non-small cell lung cancer (NSCLC). We aimed to explore the role of hsa_circ_0011298 (circ_0011298) and its mechanism in Taxol resistance of NSCLC.
Circ_0011298, microRNA-486-3p (miR-486-3p), and CRABP2 mRNA expression were determined using qRT-PCR. EdU and MTT assays were used to detect cell proliferation. Cell cycle distribution and cell apoptosis were detected by flow cytometry. Cell migratory and invasive abilities were detected using transwell assay. Cellular glycolysis was determined by specific kits. Protein levels were examined by western blot. Dual-luciferase reporter and RIP assays were performed to confirm the relationship between miR-486-3p and circ_0011298 or CRABP2. Xenograft mice model was established to confirm the function of circ_0011298 in vivo.
Circ_0011298 was overexpressed in Taxol-resistant NSCLC cells and tissues. Circ_0011298 knockdown enhanced Taxol sensitivity by decreasing cell proliferation, migration, invasion, and glycolysis and inducing apoptosis and cell cycle arrest in Taxol-resistant NSCLC cells. Circ_0011298 was a sponge of miR-486-3p, and the impact of circ_0011298 silencing on Taxol resistance was rescued by miR-486-3p inhibition. Moreover, miR-486-3p directly targeted CRABP2, and miR-486-3p inhibited Taxol resistance by targeting CRABP2. Furthermore, circ_0011298 regulated CRABP2 expression through targeting miR-486-3p. Importantly, circ_0011298 interference elevated Taxol sensitivity of NSCLC in vivo.
Circ_0011298 elevated Taxol resistance of NSCLC by sponging miR-486-3p and upregulating CRABP2, providing a possible circRNA-targeted therapy for NSCLC.
环状 RNA（circRNAs）作为人类癌症（包括非小细胞肺癌（NSCLC））化疗耐药性的关键调节剂。我们旨在探索 hsa_circ_0011298（circ_0011298）及其在紫杉醇耐药性 NSCLC 中的作用机制。
采用 qRT-PCR 检测 circ_0011298、microRNA-486-3p（miR-486-3p）和 CRABP2 mRNA 表达。采用 EdU 和 MTT 检测细胞增殖。流式细胞术检测细胞周期分布和细胞凋亡。Transwell 检测细胞迁移和侵袭能力。特定试剂盒检测细胞糖酵解。Western blot 检测蛋白水平。双荧光素酶报告和 RIP 实验证实 miR-486-3p 与 circ_0011298 或 CRABP2 的关系。建立裸鼠移植瘤模型以证实 circ_0011298 在体内的功能。
Circ_0011298 在紫杉醇耐药性 NSCLC 细胞和组织中高表达。Circ_0011298 敲低通过降低紫杉醇耐药性 NSCLC 细胞的增殖、迁移、侵袭和糖酵解，诱导细胞凋亡和细胞周期阻滞，增强紫杉醇敏感性。Circ_0011298 是 miR-486-3p 的海绵体，circ_0011298 沉默对紫杉醇耐药性的影响可通过 miR-486-3p 抑制得到挽救。此外，miR-486-3p 直接靶向 CRABP2，通过靶向 CRABP2 抑制紫杉醇耐药性。此外，circ_0011298 通过靶向 miR-486-3p 调节 CRABP2 表达。重要的是，circ_0011298 干扰可提高 NSCLC 裸鼠体内紫杉醇的敏感性。
Circ_0011298 通过海绵吸附 miR-486-3p 和上调 CRABP2 来提高 NSCLC 的紫杉醇耐药性，为 NSCLC 提供了一种可能的环状 RNA 靶向治疗方法。
