Department of Respiratory Medicine, Yiwu Fuyuan Private Hospital, Yiwu City, China.
Department of Pharmacy, Yiwu Fuyuan Private Hospital, Yiwu City, China.
Thorac Cancer. 2024 Jul;15(19):1490-1501. doi: 10.1111/1759-7714.15163. Epub 2024 May 27.
Non-small-cell lung cancer (NSCLC) is a common malignancy with high morbidity and mortality. Circular RNAs are widely involved in NSCLC progression. However, the mechanism of circSLC25A16 in NSCLC has not been reported.
The expressions of circSLC25A16, microRNA-335-5p (miR-335-5p), and CDGSH iron-sulfur domain-containing protein 2 (CISD2) were monitored by quantitative real-time fluorescence polymerase chain reaction. Western blot was also carried out to measure the protein levels of CISD2, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA). For functional analysis, cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell, and wound healing assays were utilized to examine cell proliferation, apoptosis, and migration. Glucose uptake and lactate production were detected using commercial kits. The relationship between miR-335-5p and circSLC25A16 or CISD2 was verified by dual-luciferase reporter and RNA immunoprecipitation assays. Furthermore, tumor xenograft was established to explore the function of circSLC25A16 in vivo.
CircSLC25A16 and CISD2 were overexpressed in NSCLC, but miR-335-5p was downregulated. CircSLC25A16 acted as a miR-335-5p sponge, and silencing of circSLC25A16 arrested cell proliferation, migration, and glycolysis, and promoted apoptosis, but these impacts were resumed by miR-335-5p inhibition. CISD2 was a miR-335-5p target, and overexpression of CISD2 abolished the suppressive function of miR-335-5p mimic on the malignant behavior of NSCLC cells. CircSLC25A16 could adsorb miR-335-5p to mediate CISD2 expression. Additionally, silencing circSLC25A16 restrained the growth of NSCLC tumor xenograft in vivo.
CircSLC25A16 facilitated NSCLC progression via the miR-335-5p/CISD2 axis, implying that circSLC25A16 may serve as a novel biomarker for NSCLC treatment.
非小细胞肺癌（NSCLC）是一种常见的恶性肿瘤，发病率和死亡率均较高。环状 RNA 广泛参与 NSCLC 的进展。然而，circSLC25A16 在 NSCLC 中的作用机制尚未报道。
采用实时荧光定量聚合酶链反应监测 circSLC25A16、microRNA-335-5p（miR-335-5p）和 CDGSH 铁硫域蛋白 2（CISD2）的表达。Western blot 法检测 CISD2、己糖激酶 2（HK2）和乳酸脱氢酶 A（LDHA）的蛋白水平。通过细胞计数试剂盒-8 检测、5-乙炔基-2'-脱氧尿苷、流式细胞术、Transwell 和划痕愈合实验检测细胞增殖、凋亡和迁移。使用商业试剂盒检测葡萄糖摄取和乳酸生成。通过双荧光素酶报告基因和 RNA 免疫沉淀实验验证 miR-335-5p 与 circSLC25A16 或 CISD2 的关系。此外，建立肿瘤异种移植模型以在体内探索 circSLC25A16 的功能。
circSLC25A16 和 CISD2 在 NSCLC 中高表达，而 miR-335-5p 低表达。circSLC25A16 作为 miR-335-5p 的海绵，沉默 circSLC25A16 可抑制细胞增殖、迁移和糖酵解，并促进凋亡，但 miR-335-5p 抑制可恢复这些影响。CISD2 是 miR-335-5p 的靶基因，过表达 CISD2 可消除 miR-335-5p 模拟物对 NSCLC 细胞恶性行为的抑制作用。circSLC25A16 可吸附 miR-335-5p 来调节 CISD2 的表达。此外，沉默 circSLC25A16 可抑制 NSCLC 肿瘤异种移植在体内的生长。
circSLC25A16 通过 miR-335-5p/CISD2 轴促进 NSCLC 的进展，提示 circSLC25A16 可能作为 NSCLC 治疗的新的生物标志物。
