Department of PET-CT, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Department of PET-CT, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Biochem Biophys Res Commun. 2019 Mar 12;510(3):462-466. doi: 10.1016/j.bbrc.2019.01.131. Epub 2019 Feb 2.
Non-small cell lung cancer (NSCLC) is an aggressive malignancy with poor clinical outcomes. Accumulating evidence indicated that dysregulation of circular RNAs (circRNAs) plays a key role in multiple solid tumors. In this study, circ-RAD23B was explored. The expression of circ-RAD23B in NSCLC was detected by RT-qPCR. The clinical value of circ-RAD23B was analyzed by Fisher's exact test and Kaplan-Meier curves. Gain and loss of function experiments were carried out to elucidate the biological functions of circ-RAD23B in NSCLC cell lines. Dual luciferase reporter assay and rescue experiments were used to reveal the mechanism of circ-RAD23B. The findings demonstrated that circ-RAD23B, identified to be amplified and overexpressed in NSCLC, was associated with lymph node invasion, lower differentiation grade and shorter overall survival (OS). Furthermore, circ-RAD23B functions as an oncogene in NSCLC cells. Mechanistically, circ-RAD23B could sponge miR-593-3p and miR-653-5p and thus elevate CCND2 and TIAM1 expression, respectively. Rescue assays proved that circ-RAD23B promotes cell growth via miR-593-3p/CCND2 axis and facilitates cell invasion by miR-653-5p/TIAM1 pathway. Taken together, we propose circ-RAD23B as a promising biomarker and therapeutic target for NSCLC.
非小细胞肺癌（NSCLC）是一种侵袭性恶性肿瘤，临床预后较差。越来越多的证据表明，环状 RNA（circRNAs）的失调在多种实体瘤中发挥着关键作用。在本研究中，我们探讨了 circ-RAD23B。通过 RT-qPCR 检测 NSCLC 中 circ-RAD23B 的表达。通过 Fisher 确切检验和 Kaplan-Meier 曲线分析 circ-RAD23B 的临床价值。通过 gain 和 loss of function 实验阐明 circ-RAD23B 在 NSCLC 细胞系中的生物学功能。双荧光素酶报告基因实验和挽救实验用于揭示 circ-RAD23B 的作用机制。研究结果表明，在 NSCLC 中扩增和过表达的 circ-RAD23B 与淋巴结浸润、低分化程度和总生存期（OS）缩短有关。此外，circ-RAD23B 在 NSCLC 细胞中作为癌基因发挥作用。机制上，circ-RAD23B 可以海绵吸附 miR-593-3p 和 miR-653-5p，分别上调 CCND2 和 TIAM1 的表达。挽救实验证明，circ-RAD23B 通过 miR-593-3p/CCND2 轴促进细胞生长，并通过 miR-653-5p/TIAM1 通路促进细胞侵袭。综上所述，我们提出 circ-RAD23B 作为 NSCLC 有前途的生物标志物和治疗靶点。
