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环状 RNA circ_0067934 沉默抑制非小细胞肺癌细胞的增殖、迁移和侵袭,并与非小细胞肺癌的不良预后相关。

CircRNA circ_0067934 silencing inhibits the proliferation, migration and invasion of NSCLC cells and correlates with unfavorable prognosis in NSCLC.

机构信息

Department of Thoracic surgery, Beijing Friendship Hospital, Capital Medical University, Xuanwu, Beijing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 May;22(10):3053-3060. doi: 10.26355/eurrev_201805_15063.

Abstract

OBJECTIVE

Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. The purpose of this study was to investigate the clinical significance, biological function and molecular mechanism of circ_0067934 in human non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS

We assayed expression level of circ_0067934 in NSCLC tissues and cell lines by Real-time PCR. The associations of circ_0067934 expression with clinicopathologic features and overall survival of patients with NSCLC were statistically analyzed. Biological functions of circ_0067934 were analyzed using MTT and transwell migration and invasion assays in vitro. The expression of EMT-related mRNAs and proteins was assayed using Real-time PCR and Western blot.

RESULTS

We found that circ_0067934 expression was significantly increased in NSCLC tissues and cell lines. High circ_0067934 expression was significantly associated with TNM stage (p=0.003), lymph node status (p=0.000), and distant metastasis (p=0.017). Moreover, Kaplan-Meier curves showed that higher expression of circ_0067934 led to a significantly poorer survival. Multivariate Cox proportional hazards analysis suggested that circ_0067934 was an independent poor prognostic factor for patients with NSCLC. In vitro assay indicated that down-regulation of circ_0067934 could suppress NSCLC cells proliferation, migration, and invasion. Mechanistic analysis showed that aberrant circ_0067934 expression could modulate the expression levels of markers of epithelial-to-mesenchymal transition.

CONCLUSIONS

Our data suggested that circ_0067934 functioned as an oncogenic circular RNA in NSCLC, which provided a potential prognostic biomarker and therapeutic target for NSCLC.

摘要

目的

环状 RNA 是一类非编码 RNA,由哺乳动物基因组产生。本研究旨在探讨 circ_0067934 在人非小细胞肺癌(NSCLC)中的临床意义、生物学功能和分子机制。

患者和方法

我们通过实时 PCR 检测 NSCLC 组织和细胞系中 circ_0067934 的表达水平。统计分析 circ_0067934 表达与 NSCLC 患者临床病理特征和总生存期的相关性。通过 MTT 和体外迁移和侵袭实验分析 circ_0067934 的生物学功能。通过实时 PCR 和 Western blot 检测 EMT 相关 mRNAs 和蛋白的表达。

结果

我们发现 circ_0067934 在 NSCLC 组织和细胞系中表达显著升高。高 circ_0067934 表达与 TNM 分期(p=0.003)、淋巴结状态(p=0.000)和远处转移(p=0.017)显著相关。此外,Kaplan-Meier 曲线显示,circ_0067934 表达较高导致生存显著较差。多变量 Cox 比例风险分析表明,circ_0067934 是 NSCLC 患者的独立不良预后因素。体外实验表明,下调 circ_0067934 可抑制 NSCLC 细胞的增殖、迁移和侵袭。机制分析表明,异常的 circ_0067934 表达可调节上皮-间充质转化标志物的表达水平。

结论

我们的数据表明,circ_0067934 在 NSCLC 中作为一种致癌性环状 RNA 发挥作用,为 NSCLC 提供了一个潜在的预后生物标志物和治疗靶点。

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