由STAT1介导的LINC01806通过miR-4428/NOTCH2轴的Notch信号通路促进非小细胞肺癌的细胞增殖、迁移、侵袭和干性。
LINC01806 mediated by STAT1 promotes cell proliferation, migration, invasion, and stemness in non-small cell lung cancer through Notch signaling by miR-4428/NOTCH2 axis.
作者信息
Huang Shangxiao, Liang Shixiong, Huang Jianfeng, Luo Penghui, Mo Dunchang, Wang Hanlei
机构信息
Department of Radiotherapy, The Third Affiliated Hospital of Guangxi Medical University, No.13 Dancun Road, Nanning, 530031, Guangxi, China.
Department of Radiotherapy, Cancer Hospital Affiliated to Guangxi Medical University, Nanning, 530021, Guangxi, China.
出版信息
Cancer Cell Int. 2022 May 22;22(1):198. doi: 10.1186/s12935-022-02560-8.
BACKGROUND
Non-small cell lung cancer (NSCLC), the most primary lung cancer subtype, threatens human health globally. Long non-coding RNAs (lncRNAs) have been uncovered to affect multiple cancers progression. Nevertheless, the specific function of long intergenic non-protein coding RNA 1806 (LINC01806) in NSCLC remains elusive.
METHODS
RT-qPCR and western blot were involved in this study. The influence of LINC01806 on NSCLC was assessed by in vitro and in vivo assays. Via ChIP, RNA pull down, RIP, and luciferase reporter assays, the in-depth cellular mechanisms of LINC01806 in NSCLC were explored.
RESULTS
LINC01806 expression was high in NSCLC cell lines. Functionally, LINC01806 knockdown impeded cell proliferation, migration, invasion, and stemness, along with tumor growth. As for its mechanism, signal transducer and activator of transcription 1 (STAT1) activated LINC01806 transcription in NSCLC. Furthermore, LINC01806 sequestered microRNA-4428 (miR-4428) to enhance notch receptor 2 (NOTCH2) expression, thus activating Notch signaling pathway. Finally, in vitro and in vivo assays jointly validated that LINC01806 exerted its function in NSCLC development via miR-4428/NOTCH2 pathway.
CONCLUSION
LINC01806 enhanced NOTCH2 expression to stimulate Notch signaling via sponging miR-4428, thereby facilitating NSCLC progression, which provided a novel mechanism for NSCLC therapeutic approaches.
背景
非小细胞肺癌（NSCLC）是最主要的肺癌亚型，在全球范围内威胁着人类健康。长链非编码RNA（lncRNAs）已被发现影响多种癌症的进展。然而，长链基因间非编码RNA 1806（LINC01806）在NSCLC中的具体功能仍不清楚。
方法
本研究采用逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法（western blot）。通过体外和体内实验评估LINC01806对NSCLC的影响。通过染色质免疫沉淀（ChIP）、RNA下拉、RNA免疫沉淀（RIP）和荧光素酶报告基因实验，探索LINC01806在NSCLC中的深入细胞机制。
结果
LINC01806在NSCLC细胞系中表达较高。在功能上，敲低LINC01806可抑制细胞增殖、迁移、侵袭和干性，以及肿瘤生长。至于其机制，信号转导和转录激活因子1（STAT1）激活NSCLC中LINC01806的转录。此外，LINC01806隔离微小RNA-4428（miR-4428）以增强Notch受体2（NOTCH2）的表达，从而激活Notch信号通路。最后，体外和体内实验共同验证了LINC01806通过miR-4428/NOTCH2途径在NSCLC发展中发挥作用。
结论
LINC01806通过海绵吸附miR-4428增强NOTCH2表达以刺激Notch信号通路从而促进NSCLC进展,这为NSCLC治疗方法提供了一种新机制。
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