Department of Computed Tomography, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161000, China.
Department of Imaging Equipment and Technology, Medical Technology Academy, Qiqihar Medical University, Qiqihar, 161000, China.
Biochem Biophys Res Commun. 2019 Jul 23;515(2):303-309. doi: 10.1016/j.bbrc.2019.05.158. Epub 2019 May 29.
Circular RNAs (circRNAs) is a class of non-coding RNA with important functions in tumor development and progression. In the previous study, circ_0020123 was found to be an elevated circRNA in non-small cell lung cancer (NSCLC) tissues screened by high-throughput sequencing. In the current work, we uncovered the clinical significance, biological functions and mechanism of circ_0020123 in NSCLC. The expression profile of circ_0020123 was measured by RT-qPCR. Correlations between circ_0020123 expression and patients' clinical features were evaluated. Cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), flow cytometric and transwell assay, respectively. Bioinformatics database and luciferase reporter gene assays were utilized to identify the mechanisms of circ_0020123. The results revealed elevation of circ_0020123 in tissue specimens and cells than the nontumorous tissues and 16HBE, separately. The enhancement of circ_0020123 in tumor tissues correlated with positive lymph node metastasis, advanced TNM stages, and adverse prognosis for NSCLC patients. Functionally, silencing of circ_0020123 distinctly suppressed the growth, migration and invasion and inhibited the apoptosis of A549 cells. On the contrary, when circ_0020123 expression was ectopically expressed, the above effects were significantly strengthened in H1299 cell line. For the mechanism exploration, circ_0020123 could sponge miR-488-3p to release its inhibition on ADAM9 expression. Moreover, the functional role of circ_0020123 is partly dependent on its regulation of ADAM9 proved by rescue assays. Taken together, our findings provide the possibility that circ_0020123 may be a new target for NSCLC prognosis prediction and therapy.
环状 RNA（circRNAs）是一类具有重要功能的非编码 RNA，在肿瘤的发生和发展中发挥作用。在之前的研究中，通过高通量测序筛选出非小细胞肺癌（NSCLC）组织中circ_0020123 是一种上调的环状 RNA。在本研究中，我们揭示了 circ_0020123 在 NSCLC 中的临床意义、生物学功能和机制。通过 RT-qPCR 测量 circ_0020123 的表达谱。评估 circ_0020123 表达与患者临床特征之间的相关性。通过细胞计数试剂盒-8（CCK-8）、流式细胞术和 Transwell 测定分别检测细胞活力、凋亡、迁移和侵袭。利用生物信息学数据库和荧光素酶报告基因检测来确定 circ_0020123 的机制。结果显示，circ_0020123 在组织标本和细胞中的表达高于非肿瘤组织和 16HBE，分别。肿瘤组织中 circ_0020123 的增强与阳性淋巴结转移、晚期 TNM 分期和 NSCLC 患者不良预后相关。功能上，沉默 circ_0020123 明显抑制 A549 细胞的生长、迁移和侵袭，并抑制细胞凋亡。相反，当外源性表达 circ_0020123 时，在 H1299 细胞系中上述作用显著增强。对于机制的探索，circ_0020123 可以海绵 miR-488-3p 释放其对 ADAM9 表达的抑制作用。此外，circ_0020123 的功能作用部分依赖于其对 ADAM9 的调节，这一点通过挽救实验得到证实。总之，我们的研究结果提供了一种可能性，即 circ_0020123 可能成为 NSCLC 预后预测和治疗的新靶点。
