Department of Thoracic surgery, Beijing Friendship Hospital, Capital Medical University, Xuanwu, Beijing, China.
Eur Rev Med Pharmacol Sci. 2018 May;22(10):3053-3060. doi: 10.26355/eurrev_201805_15063.
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).
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.
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.
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.
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。
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。
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。
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。