Department of Thoracic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.
Eur Rev Med Pharmacol Sci. 2020 Feb;24(3):1233-1242. doi: 10.26355/eurrev_202002_20176.
Previous studies have shown the carcinogenic role of long-chain non-coding RNAs (lncRNA) TRERNA1. However, the role of TRERNA1 in non-small cell lung cancer (NSCLC) has not been reported. This research aims to explore the regulatory effect of TRERNA1/FOXL1 axis on the malignant progression of NSCLC.
Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression levels of TRERNA1 and FOXL1 in 39 pairs of tumor tissues and paracancerous ones collected from NSCLC patients. The potential relation between TRERNA1 expression and clinical indicators of NSCLC patients was analyzed. Meanwhile, expression levels of TRERNA1 and FOXL1 in NSCLC cell lines were also detected by qRT-PCR. In addition, TRERNA1 knockdown model was constructed in H358 and SPC-A1 cells. Cell counting kit-8 (CCK-8), cell colony formation assay, and flow cytometry were applied to analyze the influence of TRERNA1 on NSCLC cell biological functions. Finally, Dual-Luciferase reporter gene assay and cell reverse recovery experiments were performed to figure out the underlying mechanisms of TRERNA1 in regulating NSCLC progression.
QRT-PCR results indicated that the expression level of lncRNA TRERNA1 in tumor tissue samples of NSCLC patients was remarkably higher than that in adjacent tissues. Compared with NSCLC patients with low expression of TRERNA1, patients with high TRERNA1 expression had a worse pathological stage and overall survival. Similarly, compared with cells in sh-NC group, the proliferation ability of cells in sh-TRERNA1 group was remarkably attenuated. In addition, cell ratio in the G1 phase increased after knockdown of TRERNA1, suggesting the arrested G1/S cell cycle. Subsequently, FOXL1 was downregulated in NSCLC cell lines and tumor tissues. Meanwhile, FOXL1 level was verified to be negatively correlated with TRERNA1 level. Additionally, the binding between TRERNA1 and FOXL1 was confirmed by Dual-Luciferase reporter gene assay. Cell reverse investigation indicated the involvement of FOXL1 in TRERNA1-regulated malignant progression of NSCLC.
LncRNA TRERNA1 was up-regulated both in NSCLC tissues and cell lines. Its level was associated with pathological stage and poor prognosis in NSCLC. In addition, lncRNA TRERNA1 could promote the malignant progression of NSCLC via modulating FOXL1.
先前的研究表明长链非编码 RNA（lncRNA）TRERNA1 具有致癌作用。然而，TRERNA1 在非小细胞肺癌（NSCLC）中的作用尚未报道。本研究旨在探讨 TRERNA1/FOXL1 轴对 NSCLC 恶性进展的调控作用。
采用实时荧光定量聚合酶链反应（qRT-PCR）检测 39 对 NSCLC 患者肿瘤组织和癌旁组织中 TRERNA1 和 FOXL1 的表达水平。分析 TRERNA1 表达与 NSCLC 患者临床指标的相关性。同时，采用 qRT-PCR 检测 NSCLC 细胞系中 TRERNA1 和 FOXL1 的表达水平。此外，构建 H358 和 SPC-A1 细胞的 TRERNA1 敲低模型。采用细胞计数试剂盒-8（CCK-8）、细胞集落形成实验和流式细胞术分析 TRERNA1 对 NSCLC 细胞生物学功能的影响。最后，通过双荧光素酶报告基因检测和细胞反向恢复实验，探讨 TRERNA1 调节 NSCLC 进展的潜在机制。
qRT-PCR 结果表明，NSCLC 患者肿瘤组织中 lncRNA TRERNA1 的表达水平明显高于癌旁组织。与 TRERNA1 低表达的 NSCLC 患者相比，TRERNA1 高表达的患者病理分期较差，总生存期较差。同样，与 sh-NC 组相比，sh-TRERNA1 组细胞的增殖能力明显减弱。此外，敲低 TRERNA1 后，细胞 G1 期比例增加，表明细胞周期停滞在 G1/S 期。随后，FOXL1 在 NSCLC 细胞系和肿瘤组织中下调。同时，FOXL1 水平与 TRERNA1 水平呈负相关。此外，通过双荧光素酶报告基因检测证实了 TRERNA1 与 FOXL1 之间的结合。细胞反向研究表明，FOXL1 参与了 TRERNA1 调节的 NSCLC 恶性进展。
lncRNA TRERNA1 在 NSCLC 组织和细胞系中均上调。其水平与 NSCLC 患者的病理分期和预后不良相关。此外，lncRNA TRERNA1 通过调节 FOXL1 促进 NSCLC 的恶性进展。
