School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Department of Clinical Laboratory, Dezhou People's Hospital, 1166 Dongfanghong Road, Decheng District, Dezhou, Shandong 253000, China.
Department of Clinical Laboratory, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China.
Life Sci. 2021 Feb 15;267:118933. doi: 10.1016/j.lfs.2020.118933. Epub 2020 Dec 23.
Non-small cell lung cancer (NSCLC) is considered a highly fatal tumor. Importantly, angiogenesis is critical for tumor progression. Long non-coding RNAs (lncRNAs), which are untranslatable, control cell functions through different pathways. lncRNA EPIC1 has been reported to promote cell viability, cell cycle progression, and invasion. However, the relationship between EPIC1 and tumor angiogenesis remains an enigma. We explored the role of EPIC1 in tumor angiogenesis in NSCLC.
First, EPIC1 expression was analyzed using the GEPIA database and was further verified using qPCR in tumor tissues from patients with NSCLC and NSCLC cell lines. Next, EPIC1 function was detected using loss-of-function and gain-of-function assays. Moreover, EdU staining, flow cytometry, and channel formation assays were performed to assess HUVEC proliferation and channel the formation in the NSCLC-HUVEC transwell co-culture system.
EPIC1 expression was significantly upregulated in NSCLC tissues and cell lines. Furthermore, the overexpression of EPIC1 in NSCLC cells stimulated HUVEC channel formation and proliferation by activating Ang2/Tie2 signaling, and the opposite results were obtained when EPIC1 was silenced in NSCLC cells. The density of new blood vessels was simultaneously increased by EPIC1 overexpression in vivo, using CAM angiogenesis model and a nude mouse tumor model. Finally, all these experimental findings could be established in the samples from patients with NSCLC. We postulate that EPIC1 promotes tumor angiogenesis by activating the Ang2/Tie2 axis in NSCLC.
Elucidating the molecular and cellular mechanisms of EPIC1 in tumor angiogenesis provides a novel perspective on NSCLC clinical therapy.
非小细胞肺癌（NSCLC）被认为是一种高度致命的肿瘤。重要的是，血管生成对于肿瘤的进展至关重要。长链非编码 RNA（lncRNA）是不可翻译的，通过不同的途径控制细胞功能。已有报道称 lncRNA EPIC1 可促进细胞活力、细胞周期进程和侵袭。然而，EPIC1 与肿瘤血管生成之间的关系仍然是一个谜。我们探讨了 EPIC1 在 NSCLC 肿瘤血管生成中的作用。
首先，使用 GEPIA 数据库分析 EPIC1 的表达，并在 NSCLC 患者的肿瘤组织和 NSCLC 细胞系中使用 qPCR 进一步验证。接下来，使用功能丧失和功能获得实验检测 EPIC1 的功能。此外，进行 EdU 染色、流式细胞术和通道形成实验，以评估 NSCLC-HUVEC 转染共培养系统中 HUVEC 的增殖和通道形成。
EPIC1 在 NSCLC 组织和细胞系中表达显著上调。此外，在 NSCLC 细胞中过表达 EPIC1 可通过激活 Ang2/Tie2 信号通路刺激 HUVEC 通道形成和增殖，而在 NSCLC 细胞中沉默 EPIC1 则获得相反的结果。在体内 CAM 血管生成模型和裸鼠肿瘤模型中，过表达 EPIC1 可同时增加新血管的密度。最后，在 NSCLC 患者的样本中可以证实所有这些实验发现。我们推测，EPIC1 通过在 NSCLC 中激活 Ang2/Tie2 轴促进肿瘤血管生成。
阐明 EPIC1 在肿瘤血管生成中的分子和细胞机制为 NSCLC 临床治疗提供了新的视角。
