Department of Thoracic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China.
Qingdao University, Qingdao, Shandong 266071, China.
Biomed Res Int. 2022 Jul 8;2022:7162623. doi: 10.1155/2022/7162623. eCollection 2022.
This study focused on the biological functions and mechanisms of action of LINC01554 in nonsmall cell lung cancer (NSCLC).
The expression and prognostic values of LINC01554 in NSCLC were evaluated using The Cancer Genome Atlas datasets. MTT, colony formation, wound healing, transwell, and in vivo assays were performed to investigate the role of LINC01554 in NSCLC. The related protein expression levels were measured via western blotting. Bioinformatic analysis was conducted to predict targeted genes. The relationship between LINC01554, microRNA- (miR-) 1267, miR-1267, and inhibitor of growth family member 3 (ING3) was analysed via a dual-luciferase reporter assay.
LINC01554 expression was downregulated in NSCLC and associated with NSCLC prognosis. LINC01554 overexpression suppressed NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Bioinformatic and dual-luciferase reporter assays demonstrated that LINC01554 expression directly targeted miR-1267 expression, which in turn directly acted on ING3. An miR-1267 mimic significantly reduced ING3 expression, whereas an miR-1267 inhibitor observably elevated its expression. LINC01554 overexpression increased ING3 expression, whereas this effect was counteracted by the miR-1267 mimic. LINC01554 overexpression also significantly suppressed the expression of phosphorylated protein kinase B (Akt) and phosphorylated mammalian target of rapamycin (mTOR) expression; this effect was abrogated by the miR-1267 mimic. Mechanistically, LINC01554 overexpression repressed the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells through the regulation of the miR-1267/ING3 axis via regulation of the Akt/mTOR signalling pathway.
We provide the first evidence of the involvement of the LINC01554/miR-1267 axis in NSCLC proliferation and metastasis through the ING3Akt/mTOR pathway. Thus, LINC01554 may serve as a novel therapeutic target for NSCLC.
本研究旨在探讨 LINC01554 在非小细胞肺癌（NSCLC）中的生物学功能和作用机制。
使用癌症基因组图谱（TCGA）数据集评估 LINC01554 在 NSCLC 中的表达和预后价值。通过 MTT、集落形成、划痕愈合、Transwell 和体内实验研究 LINC01554 在 NSCLC 中的作用。通过 Western blot 测定相关蛋白表达水平。进行生物信息学分析以预测靶向基因。通过双荧光素酶报告基因实验分析 LINC01554、microRNA-（miR-）1267、miR-1267 和生长抑制因子家族成员 3（ING3）之间的关系。
LINC01554 在 NSCLC 中表达下调，并与 NSCLC 预后相关。LINC01554 过表达抑制 NSCLC 细胞增殖、迁移、侵袭和上皮-间充质转化（EMT）。生物信息学和双荧光素酶报告基因实验表明，LINC01554 表达直接靶向 miR-1267 表达，而 miR-1267 又直接作用于 ING3。miR-1267 模拟物显著降低 ING3 表达，而 miR-1267 抑制剂则明显升高其表达。LINC01554 过表达增加 ING3 表达，而 miR-1267 模拟物则拮抗这一作用。LINC01554 过表达还显著抑制磷酸化蛋白激酶 B（Akt）和磷酸化哺乳动物雷帕霉素靶蛋白（mTOR）的表达；而 miR-1267 模拟物则消除了这一作用。在机制上，LINC01554 过表达通过调节 Akt/mTOR 信号通路，通过调节 miR-1267/ING3 轴，抑制 NSCLC 细胞的生长、迁移、侵袭和上皮-间充质转化（EMT）。
我们首次提供了证据表明，LINC01554 通过调节 Akt/mTOR 信号通路，通过 miR-1267/ING3 轴参与 NSCLC 增殖和转移，LINC01554 可能成为 NSCLC 的一种新的治疗靶点。
