长链非编码 RNA AL139294.1 可以通过细胞外囊泡进行转运，通过激活非小细胞肺癌中的 Wnt 和 NF-κB2 通路，促进受体细胞的致癌行为。
LncRNA AL139294.1 can be transported by extracellular vesicles to promote the oncogenic behaviour of recipient cells through activation of the Wnt and NF-κB2 pathways in non-small-cell lung cancer.
机构信息
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, 818 Fenghua Road, Ningbo, Zhejiang, 315211, China.
Zhejiang Provincial Key Laboratory of Pathophysiology, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China.
出版信息
J Exp Clin Cancer Res. 2024 Jan 16;43(1):20. doi: 10.1186/s13046-023-02939-z.
BACKGROUND
Extracellular vesicles (EVs) participate in cancer development via cell-to-cell communication. Long non-coding RNAs (lncRNAs), one component of EVs, can play an essential role in non-small-cell lung cancer (NSCLC) through EV-mediated delivery.
METHODS
The NSCLC-associated lncRNA AL139294.1 in EVs was identified via lncRNA microarray analysis. The role of AL139294.1 in NSCLC was examined in vitro and in vivo. Confocal microscopy was used to observe the encapsulation of AL139294.1 into EVs and its transport to recipient cells. A co-culture device was used to examine the effects of transported AL139294.1 on the oncogenic behaviour of recipient cells. Dual-luciferase reporter assay was performed to verify the direct interaction of miR-204-5p with AL139294.1 and bromodomain-containing protein 4 (BRD4). AL139294.1 and miR-204-5p in EVs were quantified using quantitative polymerase chain reaction. Receiver operating characteristic analyses were conducted to evaluate the diagnostic efficiency.
RESULTS
The lncRNA AL139294.1 in EVs promoted NSCLC progression in vitro and in vivo. After AL139294.1 was encapsulated into EVs and transported to recipient cells, it promoted the cells' proliferation, migration, and invasion abilities by competitively binding with miR-204-5p to regulate BRD4, leading to the activation of the Wnt and NF-κB2 pathways. Additionally, the expression of serum lncRNA AL139294.1 in EVs was increased, whereas miR-204-5p in EVs was decreased in NSCLC. High levels of lncRNA AL139294.1 and low levels of miR-204-5p in EVs were associated with advanced pathological staging, lymph node metastasis, and distant metastasis, underscoring their promising utility for distinguishing between more and less severe manifestations of the disease.
CONCLUSIONS
This study reveals a novel lncRNA in EVs associated with NSCLC, namely, AL139294.1, providing valuable insights into the development of NSCLC and introducing potential diagnostic biomarkers for NSCLC.
背景
细胞外囊泡（EVs）通过细胞间通讯参与癌症的发生。长链非编码 RNA（lncRNA）是 EV 的一个组成部分，可通过 EV 介导的递送来在非小细胞肺癌（NSCLC）中发挥重要作用。
方法
通过 lncRNA 微阵列分析鉴定出与 NSCLC 相关的 EV 中的 lncRNA AL139294.1。在体外和体内研究了 AL139294.1 在 NSCLC 中的作用。共聚焦显微镜用于观察 AL139294.1 被包裹到 EV 中并被运送到受体细胞的情况。使用共培养装置来研究被运输的 AL139294.1 对受体细胞致癌行为的影响。双荧光素酶报告实验验证 miR-204-5p 与 AL139294.1 和溴结构域蛋白 4（BRD4）之间的直接相互作用。使用定量聚合酶链反应检测 EV 中的 AL139294.1 和 miR-204-5p。进行接收者操作特征分析来评估诊断效率。
结果
EV 中的 lncRNA AL139294.1 促进了 NSCLC 的体外和体内进展。AL139294.1 被包裹到 EV 中并被运送到受体细胞后，通过与 miR-204-5p 竞争结合来调节 BRD4，从而促进细胞的增殖、迁移和侵袭能力，导致 Wnt 和 NF-κB2 通路的激活。此外，NSCLC 患者血清 EV 中的 lncRNA AL139294.1 表达增加，而 EV 中的 miR-204-5p 表达降低。EV 中高水平的 lncRNA AL139294.1 和低水平的 miR-204-5p 与晚期病理分期、淋巴结转移和远处转移相关，这突出了它们在区分疾病严重程度方面的潜在应用价值。
结论
本研究揭示了一种与 NSCLC 相关的新型 EV 中的 lncRNA，即 AL139294.1，为 NSCLC 的发生提供了有价值的见解，并为 NSCLC 引入了潜在的诊断生物标志物。
Zotero 插件