环状 RNA 0026134 通过 miR-3619-5p/CHAF1B 轴促进 NSCLC 的进展。
Circ_0026134 promotes NSCLC progression by the miR-3619-5p/CHAF1B axis.
机构信息
Department of Respiratory and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.
出版信息
Thorac Cancer. 2022 Feb;13(4):582-592. doi: 10.1111/1759-7714.14301. Epub 2022 Jan 5.
BACKGROUND
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Circular RNAs (circRNAs) have been implicated in the pathogenesis of NSCLC. In this study, we explored the molecular determinants underlying the oncogenic property of circ_0026134 in NSCLC.
METHODS
The levels of circ_0026134, miR-3619-5p and chromatin assembly factor 1 subunit B axis (CHAF1B) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell colony formation, migration, invasion and apoptosis were detected by colony formation, Transwell, and flow cytometry assays, respectively. Direct relationships among circ_0026134, miR-3619-5p and CHAF1B were verified by dual-luciferase reporter assays.
RESULTS
Our results showed that circ_0026134 was highly expressed in NSCLC tissues and cells. Reduced circ_0026134 expression or miR-3619-5p overexpression inhibited NSCLC cell colony formation, migration, invasion, glycolysis and promoted cell apoptosis in vitro. Moreover, circ_0026134 directly targeted miR-3619-5p, and circ_0026134 regulated CHAF1B expression through miR-3619-5p. CHAF1B was a downstream effector of circ_0026134 in affecting NSCLC cell functional behaviors in vitro. Additionally, circ_0026134 silencing weakened tumor growth in vivo.
CONCLUSIONS
Our study identified a novel regulatory mechanism, the circ_0026134/miR-3619-5p/CHAF1B axis, for the oncogenic role of circ_0026134 in NSCLC, highlighting circ_00261345 inhibition as a potential therapeutic method against NSCLC.
背景
非小细胞肺癌（NSCLC）是全球癌症死亡的主要原因。环状 RNA（circRNAs）已被认为与 NSCLC 的发病机制有关。在这项研究中，我们探讨了 circ_0026134 在 NSCLC 致癌性中的分子决定因素。
方法
通过定量实时聚合酶链反应（qRT-PCR）和 Western blot 评估 circ_0026134、miR-3619-5p 和染色质组装因子 1 亚基 B 轴（CHAF1B）的水平。通过集落形成、Transwell 和流式细胞术分别检测细胞集落形成、迁移、侵袭和凋亡。通过双荧光素酶报告基因实验验证 circ_0026134、miR-3619-5p 和 CHAF1B 之间的直接关系。
结果
我们的结果表明，circ_0026134 在 NSCLC 组织和细胞中高度表达。降低 circ_0026134 表达或过表达 miR-3619-5p 可抑制 NSCLC 细胞集落形成、迁移、侵袭、糖酵解并促进细胞凋亡。此外，circ_0026134 直接靶向 miR-3619-5p，circ_0026134 通过 miR-3619-5p 调节 CHAF1B 的表达。CHAF1B 是 circ_0026134 在体外影响 NSCLC 细胞功能行为的下游效应物。此外，circ_0026134 沉默减弱了体内肿瘤生长。
结论
我们的研究确定了一个新的调控机制，circ_0026134/miR-3619-5p/CHAF1B 轴，circ_0026134 在 NSCLC 中的致癌作用，强调抑制 circ_0026134 可能是治疗 NSCLC 的一种潜在方法。
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