Long noncoding RNA CRNDE promotes non-small cell lung cancer progression via sponging microRNA-338-3p
Long noncoding RNA CRNDE promotes non-small cell lung cancer progression via sponging microRNA-338-3p
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DOI：
10.1016/j.biopha.2018.12.024
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发表时间：
2019-02-01
影响因子：
7.5
通讯作者：
Lv, Xiaohong
中科院分区：
文献类型：
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作者：
Jing, Hongyu;Xia, Huan;Lv, Xiaohong
背景：据报道，长链非编码RNA结直肠癌差异表达（CRNDE）参与多种癌症的发生和发展。然而，CRNDE在非小细胞肺癌（NSCLC）中的详细生物学作用在很大程度上仍不清楚。在此，我们旨在探讨CRNDE在NSCLC中的生物学功能和潜在的分子机制。材料与方法：采用定量实时聚合酶链反应（Quantitative real-lime polymerase chain reaction, qRT-PCR）检测CRNDE在NSCLC组织和细胞系中的表达。细胞计数试剂盒-8 （CCK-8）、菌落形成、流式细胞术、伤口愈合和transwell侵袭实验分别检测细胞增殖、菌落形成、周期阻滞进展、迁移和侵袭。利用生物信息学软件选择新的CRNDE靶点，并通过荧光素酶报告基因和RNA免疫沉淀实验进行确认。为了检测CRNDE在体内肿瘤发生中的作用，我们建立了肿瘤异种移植物。结果：CRNDE在非小细胞肺癌组织和细胞系中表达显著上调。CRNDE表达上调与NSCLC患者的晚期肿瘤-淋巴结转移（TNM）分期、淋巴结转移和较差的总生存率呈正相关。功能实验表明，敲低CRNDE可显著抑制非小细胞肺癌细胞的体外增殖、集落形成、迁移和侵袭，减少体外移植瘤的体积和重量。我们发现miR-338-3p是CRNDE的下游靶点，miR-338-3p抑制部分逆转了CRNDE耗尽介导的对NSCLC细胞增殖、集落形成、迁移和侵袭的抑制作用。结论：这些发现表明CRNDE作为一个癌基因，通过海绵miR-338-3p在NSCLC的进展中发挥重要的调节作用。
Background: The long noncoding RNA colorectal neoplasia differentially expressed (CRNDE) was reported to be involved in the initiation and development of multiple cancers. However, the detailed biological role of CRNDE in non-small cell lung cancer (NSCLC) remains largely unclear. Herein, we aimed to explore the biological function and underlying molecular mechanism of CRNDE in NSCLC.Materials and methods: Quantitative real-lime polymerase chain reaction (qRT-PCR) was employed to detect the expression of CRNDE in NSCLC tissues and cell lines. Cell counting kit-8 (CCK-8), colony formation, flow cytometry, wound-healing, and transwell invasion assays were applied to detect cell proliferation, colony formation, cycle arrest progression, migration and invasion, respectively. Novel targets of CRNDE were selected with bioinformatics software and were confirmed using luciferase reporter and RNA immunoprecipitation assays. To detect the role of CRNDE in vivo tumorigenesis, tumor xenografts were created.Results: CRNDE expression is remarkably upregulated in NSCLC tissues and cell lines. Upregulated CRNDE expression was positively associated with advanced tumor-node-metastasis (TNM) stage, lymph node metastasis and poor overall survival of patients with NSCLC. Function assays demonstrated that knockdown of CRNDE significantly inhibited NSCLC cell proliferation, colony formation, migration and invasionin vitro, and decreased the xenograft tumor volume and weight in vitro. We uncovered that miR-338-3p is a downstream target of CRNDE and that miR-338-3p inhibition partially reversed the CRNDE depletion-mediated inhibitory effect on cell proliferation, colony formation, migration and invasion in NSCLC cells.Conclusion: These findings indicated that CRNDE functions as an oncogene that exerts important regulatory roles in NSCLC progression via sponging miR-338-3p.