Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, China.
Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, PR China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):185-192. doi: 10.1016/j.bbrc.2018.11.004. Epub 2018 Nov 16.
Evidence has shown the importance of long non-coding RNAs (lncRNAs) during angiogenesis and lung cancer progression. However, the potential functions of TNK2-AS1 in non-small cell lung cancer (NSCLC) remain elusive. By lncRNA profiling, we identified TNK2-AS1 as a novel oncogenic lncRNA in NSCLC. TNK2-AS1 was significantly upregulated in NSCLC and correlated with poor prognosis. We found that TNK2-AS1 could increase viability and migration of NSCLC cells in vitro. TNK2-AS1 also promoted NSCLC xenograft tumor growth and metastasis in vivo. TNK2-AS1 could interact with STAT3 to increase its protein stability by protecting it from proteasome-mediated degradation. STAT3 could also bind TNK2-AS1 promoter to trigger its transcription. The positive feedback loop between STAT3 and TNK2-AS1 therefore augmented STAT3 signaling by elevating VEGFA expression to facilitate angiogenesis. Collectively, our work has elucidated a novel mechanism of TNK2-AS1-mediated angiogenesis by enforcing STAT3/VEGFA signaling and may provide a potential target for therapeutic intervention.
已有证据表明长链非编码 RNA（lncRNA）在血管生成和肺癌进展过程中的重要性。然而，TNK2-AS1 在非小细胞肺癌（NSCLC）中的潜在功能仍不清楚。通过 lncRNA 谱分析，我们发现 TNK2-AS1 是 NSCLC 中的一种新型致癌 lncRNA。TNK2-AS1 在 NSCLC 中显著上调，并与不良预后相关。我们发现 TNK2-AS1 可以增加 NSCLC 细胞在体外的活力和迁移能力。TNK2-AS1 还可以促进 NSCLC 异种移植肿瘤的生长和转移。TNK2-AS1 可以与 STAT3 相互作用，通过保护其免受蛋白酶体介导的降解来增加其蛋白质稳定性。STAT3 也可以结合 TNK2-AS1 启动子来触发其转录。因此，STAT3 和 TNK2-AS1 之间的正反馈循环通过提高 VEGFA 的表达来增强 STAT3 信号，从而促进血管生成。综上所述，我们的工作阐明了 TNK2-AS1 介导的血管生成的新机制，通过增强 STAT3/VEGFA 信号，可能为治疗干预提供潜在的靶点。
