环状 RNA circP4HB 通过海绵吸附 miR-133a-5p 促进 NSCLC 的侵袭和转移。
The circRNA circP4HB promotes NSCLC aggressiveness and metastasis by sponging miR-133a-5p.
机构信息
Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui Province, China.
Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, Department of Respiration, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui Province, China.
出版信息
Biochem Biophys Res Commun. 2019 Jun 11;513(4):904-911. doi: 10.1016/j.bbrc.2019.04.108. Epub 2019 Apr 17.
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.
背景
非小细胞肺癌（NSCLC）仍然位居全球癌症死亡率之首。环状 RNA（circRNAs）在肿瘤发生中的作用越来越受到重视，尽管在 NSCLC 中相对尚未得到充分研究。本文报告了 circP4HB 在 NSCLC 中的作用。
方法
首先，我们评估了患者来源的 NSCLC 组织与配对的健康样本中的 circP4HB 水平。接下来，我们在 NSCLC 细胞系中进行了体外实验，并在小鼠异种移植 NSCLC 模型中进行了体内实验，以评估 circP4HB 对体外上皮-间充质转化（EMT）和体内转移的影响。还评估了 circP4HB 对 microRNA miR-133a-5p 及其 EMT 标志物波形蛋白的下游影响。
结果
与配对的健康肺组织相比，NSCLC 肿瘤标本中 circP4HB 水平升高，与转移性疾病和较差的生存相关。circP4HB 通过结合 miR-133a-5p 促进 EMT 和体外 vimentin 表达以及体内异种移植转移。
结论
circP4HB 通过结合 miR-133a-5p 促进 EMT 和转移性疾病，从而上调波形蛋白。因此，这些发现表明靶向 circP4HB/miR-133a-5p/波形蛋白轴可能是 NSCLC 患者的潜在治疗选择。
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