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Abstract：
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.
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.
摘要：
背景：细胞外囊泡（EV）通过细胞与细胞的通讯参与癌症的发展。长链非编码RNA（lncRNA），电动汽车的一个组成部分，可以通过EV介导的递送在非小细胞肺癌（NSCLC）中发挥重要作用。
方法：通过lncRNA微阵列分析鉴定了EV中NSCLC相关的lncRNAAL139294.1。在体外和体内检查了AL139294.1在NSCLC中的作用。使用共聚焦显微镜观察AL139294.1在EV中的包封及其向受体细胞的转运。使用共培养装置来检查运输的AL139294.1对受体细胞的致癌行为的影响。进行双荧光素酶报告基因测定以验证miR-204-5p与AL139294.1和含溴结构域蛋白4(BRD4)的直接相互作用。使用定量聚合酶链反应对电动汽车中的AL139294.1和miR-204-5p进行定量。进行了接收器工作特性分析以评估诊断效率。
结果：EV中的lncRNAAL139294.1在体外和体内促进NSCLC进展。将AL139294.1封装到EV中并转运到受体细胞后，它促进了细胞的增殖，迁移,和侵袭能力通过与miR-204-5p竞争性结合来调节BRD4，导致Wnt和NF-κB2途径的激活。此外,血清lncRNAAL139294.1在电动汽车中的表达增加，而miR-204-5p在EV中在NSCLC中降低。EV中高水平的lncRNAAL139294.1和低水平的miR-204-5p与晚期病理分期相关，淋巴结转移,和远处转移，强调了它们在区分疾病的严重表现方面的有希望的效用。
结论：这项研究揭示了与NSCLC相关的EV中的一种新型lncRNA，即,AL139294.1，为NSCLC的发展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。
方法：通过lncRNA微阵列分析鉴定了EV中NSCLC相关的lncRNAAL139294.1。在体外和体内检查了AL139294.1在NSCLC中的作用。使用共聚焦显微镜观察AL139294.1在EV中的包封及其向受体细胞的转运。使用共培养装置来检查运输的AL139294.1对受体细胞的致癌行为的影响。进行双荧光素酶报告基因测定以验证miR-204-5p与AL139294.1和含溴结构域蛋白4(BRD4)的直接相互作用。使用定量聚合酶链反应对电动汽车中的AL139294.1和miR-204-5p进行定量。进行了接收器工作特性分析以评估诊断效率。
结果：EV中的lncRNAAL139294.1在体外和体内促进NSCLC进展。将AL139294.1封装到EV中并转运到受体细胞后，它促进了细胞的增殖，迁移,和侵袭能力通过与miR-204-5p竞争性结合来调节BRD4，导致Wnt和NF-κB2途径的激活。此外,血清lncRNAAL139294.1在电动汽车中的表达增加，而miR-204-5p在EV中在NSCLC中降低。EV中高水平的lncRNAAL139294.1和低水平的miR-204-5p与晚期病理分期相关，淋巴结转移,和远处转移，强调了它们在区分疾病的严重表现方面的有希望的效用。
结论：这项研究揭示了与NSCLC相关的EV中的一种新型lncRNA，即,AL139294.1，为NSCLC的发展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。
