环状 RNA circ_0003645 的升高通过 miR-1179/TMEM14A 通路预测非小细胞肺癌的不良预后并促进细胞进展。
Elevation of circular RNA circ_0003645 forecasts unfavorable prognosis and facilitates cell progression via miR-1179/TMEM14A pathway in non-small cell lung cancer.
机构信息
Department of Respiratory Medicine, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.
Department of Personnel, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.
出版信息
Biochem Biophys Res Commun. 2019 Apr 16;511(4):921-925. doi: 10.1016/j.bbrc.2019.03.011. Epub 2019 Mar 8.
BACKGROUND
Non-small cell lung cancer (NSCLC) is a highly aggressive malignancy with increasing incidence across the world. The role and mechanism of circular RNAs (circRNAs) in the pathogenesis of NSCLC have not been understood exactly. In this work, we aims to explore a novel NSCLC-associated circRNA, circ_0003645.
METHODS
The expression profile of circ_0003645 was evaluated in NSCLC tissue specimens and cells. Additionally, the correlation between circ_0003645 and clinical features/patients' prognosis were investigated. Functionally, CCK-8, clone formation, flow cyometric and transwell assays were performed in two cell lines. Furthermore, dual-luciferase reporter and rescue experiments were carried out to elucidate the mechanism of circ_0003645.
RESULTS
The data demonstrated an upregulation of circ_0003645 in patients' tissue specimens and cells. Overexpression of circ_0003645 in tissues was related to advanced TNM stages, positive lymph node invasion and unfavorable prognosis for the patients with NSCLC. In addition, gain and loss of function assays uncovered that circ_0003645 functioned as an oncogene in NSCLC cells. Moreover, circ_0003645 acted as a ceRNA to sponge miR-1179, which resulted in the elevation of TMEM14A expression and facilitated cell progression.
CONCLUSIONS
This study indicates that circ_0003645 might possess crucial potential as a prognosis predictor and therapeutic target for NSCLC patients.
背景
非小细胞肺癌（NSCLC）是一种具有侵袭性的恶性肿瘤，其发病率在全球范围内呈上升趋势。环状 RNA（circRNA）在 NSCLC 发病机制中的作用和机制尚未完全阐明。在这项工作中，我们旨在探索一种新型 NSCLC 相关的 circRNA，circ_0003645。
方法
评估了 circ_0003645 在 NSCLC 组织标本和细胞中的表达谱。此外，还研究了 circ_0003645 与临床特征/患者预后的相关性。在两种细胞系中，通过 CCK-8、克隆形成、流式细胞术和 Transwell 检测进行了功能研究。此外，还进行了双荧光素酶报告和挽救实验，以阐明 circ_0003645 的作用机制。
结果
数据表明，circ_0003645 在患者组织标本和细胞中的表达上调。circ_0003645 在组织中的过表达与晚期 TNM 分期、阳性淋巴结浸润和 NSCLC 患者的不良预后相关。此外，功能获得和功能丧失实验表明，circ_0003645 在 NSCLC 细胞中作为癌基因发挥作用。此外，circ_0003645 作为 ceRNA 可以吸附 miR-1179，导致 TMEM14A 表达升高，促进细胞进展。
结论
本研究表明，circ_0003645 可能作为 NSCLC 患者的预后预测因子和治疗靶点具有重要的潜在价值。
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