The circRNA circP4HB promotes NSCLC aggressiveness and metastasis by sponging miR-133a-5p
The circRNA circP4HB promotes NSCLC aggressiveness and metastasis by sponging miR-133a-5p
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DOI：
10.1016/j.bbrc.2019.04.108
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发表时间：
2019-06-11
影响因子：
3.1
通讯作者：
Wang, Xiaojing
中科院分区：
文献类型：
--
作者：
Wang, Tao;Wang, Xiaoxu;Wang, Xiaojing
背景：非小细胞肺癌（NSCLC）继续位居全球癌症死亡率之首。环状 RNA (circRNA) 在肿瘤发生中的作用越来越受到重视，尽管它在 NSCLC 中的研究相对较少。在此，我们报告了 circP4HB 在 NSCLC 中的作用。方法：首先，我们评估了患者来源的 NSCLC 组织与配对健康样本中的 circP4HB 水平。接下来，我们在 NSCLC 细胞系中进行体外实验，并在小鼠异种移植 NSCLC 模型中进行体内实验，以评估 circP4HB 对体外上皮间质转化 (EMT) 和体内转移的影响。还评估了 circP4HB 对 microRNA miR-133a-5p 及其靶点 EMT 标记波形蛋白的下游影响。结果：与配对的健康肺样本相比，NSCLC 肿瘤样本表现出更高的 circP4HB 水平，并且与转移性疾病和较差的生存率相关。 circP4HB 通过隔离 miR-133a-5p 促进体外 EMT 和波形蛋白表达以及体内异种移植转移。结论：circP4HB 通过隔离 miR-133a-5p 增强 EMT 和转移性疾病，导致波形蛋白上调。因此，这些发现主张将 circP4HB/miR-133a-5p/波形蛋白轴作为针对 NSCLC 患者的潜在治疗选择。 (C) 2019 Elsevier Inc. 保留所有权利。
Background: Non-small cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we report on the role of circP4HB in NSCLC.Methods: First, we evaluated circP4HB levels in patient-derived NSCLC tissue versus paired healthy samples. Next, we conducted experiments in vitro in NSCLC cell-lines and in vivo in a murine xenograft NSCLC model to assess the impact of circP4HB on epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo. The downstream impact of circP4HB on the microRNA miR-133a-5p, and its target the EMT marker vimentin, were also evaluated.Results: NSCLC tumor specimens exhibited higher circP4HB levels in comparison to paired healthy lung samples and was associated with metastatic disease and poorer survival. circP4HB promoted EMT and vimentin expression in vitro and xenograft metastasis in vivo through sequestration of miR-133a-5p.Conclusion: circP4HB enhances EMT and metastatic disease through miR-133a-5p sequestration, leading to upregulation of vimentin. Therefore, these findings advocate targeting the circP4HB/miR-133a-5p/vimentin axis as a potential therapeutic option for NSCLC patients. (C) 2019 Elsevier Inc. All rights reserved.