The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
The circRNA circPTPRA suppresses epithelial-mesenchymal transitioning and metastasis of NSCLC cells by sponging miR-96-5p
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DOI：
10.1016/j.ebiom.2019.05.032
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发表时间：
2019-06-01
期刊：
影响因子：
11.1
通讯作者：
Li, Wei
中科院分区：
文献类型：
--
作者：
Wei, Siliang;Zheng, Yuanyuan;Li, Wei
背景：非小细胞肺癌（NSCLC）是一种常见的致死性癌症，由于晚期发现和化疗耐药，前景尤其严峻。环状rna （circRNAs）是参与肿瘤发展的非编码rna。然而，环状rna在非小细胞肺癌中的作用尚不清楚。本研究探讨了circRNA circPTPRA在NSCLC中的作用，并对其作用的分子机制进行了表征。方法：分析circPTPRA在人非小细胞肺癌肿瘤和匹配的健康肺组织中的表达。我们在非小细胞肺癌细胞系和非小细胞肺癌小鼠异种移植模型中进行了功能表征，以阐明环cptpra在上皮-间质转化（EMT）中的分子作用。我们还评估了circPTPRA对microRNA miR-96-5p及其靶点肿瘤抑制因子Ras关联域蛋白8 （RASSF8）的调控作用。结果：相对于匹配的健康肺组织，环状cftpra在NSCLC肿瘤中显著下调。较低的circFTPRA水平与NSCLC患者的转移和较差的生存结果相关。circPTPRA通过隔离miR-96-5p和上调RASSF8抑制NSCLC细胞系的EMT，并减少小鼠异种移植物模型的转移。患者源性NSCLC肿瘤标本的相关分析支持circlITPRA/miR-96-5p/RASSF8/E-cadherin轴异常参与NSCLC肿瘤进展。解释：circPTPRA通过海绵miR-96-5p抑制NSCLC细胞系的EMT和转移，miR-96-5p上调下游肿瘤抑制因子RASSF8。circPTPRA/miR-96-5p/RASSF8/E-cadherin轴可以作为非小细胞肺癌的潜在治疗途径。(C) 2019作者。Elsevier B.V.出版
Background: Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well known. This study investigated the role of one circRNA - circPTPRA- in NSCLC and characterized its molecular mechanism of action.Methods: circPTPRA expression was analyzed in human NSCLC tumors and matched healthy lung tissue. We performed functional characterization in NSCLC cell lines and a mouse xenograft model of NSCLC to elucidate the molecular role of circPTPRA in epithelial-mesenchymal transitioning (EMT). We also assessed the regulatory action of circPTPRA on the microRNA miR-96-5p and its target the tumor suppressor Ras association domaincontaining protein 8 (RASSF8).Findings: circFTPRA was significantly downregulated in NSCLC tumors relative to matched healthy lung tissue. Lower circFTPRA levels correlated with metastasis and inferior survival outcomes in NSCLC patients. circPTPRA suppressed EMT in NSCLC cell lines and reduced metastasis in the murine xenograft model by sequestering miR-96-5p and upregulating RASSF8. Correlation analyses in patient-derived NSCLC tumor specimens supported the involvement of the circlITPRA/miR-96-5p/RASSF8/E-cadherin axis dysregulation in NSCLC tumor progression.Interpretation: circPTPRA suppresses EMT and metastasis of NSCLC cell lines by sponging miR-96-5p, which upregulates the downstream tumor suppressor RASSF8. The circPTPRA/miR-96-5p/RASSF8/E-cadherin axis can be leveraged as a potential treatment avenue in NSCLC. (C) 2019 The Authors. Published by Elsevier B.V.