Department of Respiratory, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland).
Department of Respiratory, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China (mainland).
Med Sci Monit. 2020 Jun 8;26:e921200. doi: 10.12659/MSM.921200.
BACKGROUND Circular RNAs (circRNAs) are frequently aberrantly expressed in non-small cell lung cancer (NSCLC) and are considered to exert a pivotal role in the occurrence and development of NSCLC via targeting and negatively regulating microRNAs (miRNAs). We aimed to investigate the role of hsa_circ_0109320 in the proliferation, invasion and apoptosis of NSCLC, and explore its underlying molecular mechanism. MATERIAL AND METHODS Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the circ_0109320 and miR-595 expression in tissues or cells. Western blot analysis was conducted to examine the cleaved caspase-3, Bax, Bcl-2, and E2F7 protein expression. Transwell detection was used to evaluate the invasion level of NSCLC cell lines. RESULTS The results of present study indicated that circ_0109320 expression in NSCLC patients was upregulated significantly in tumor tissues compared with tissues adjacent to carcinoma. Upregulated circ_0109320 level was significantly associated with TNM stages as well as lymph node metastasis of NSCLC. Moreover, downregulation of circ_0109320 attenuated proliferation and invasion while promoting apoptosis in NSCLC cells. We further confirmed that circ_0109320 could sponge miR-595 to upregulate E2F7 expression. Silencing of miR-595 or overexpression of E2F2 could partially reversed the inhibitory role of circ_0109320 knockdown in NSCLC cells. These data provided evidence that the suppression of circ_0109320 attenuates NSCLC cell proliferation and invasion and enhances apoptosis through the miR-595/E2F7 pathway. CONCLUSIONS Circ_0109320/miR-595/E2F2 axis may exert a pivotal role in the pathological mechanism of NSCLC progression, and it has potential application in the future treatment of NSCLC.
环状 RNA（circRNAs）在非小细胞肺癌（NSCLC）中经常异常表达，被认为通过靶向和负调控 microRNA（miRNA）在 NSCLC 的发生和发展中发挥关键作用。我们旨在研究 hsa_circ_0109320 在 NSCLC 增殖、侵袭和凋亡中的作用，并探讨其潜在的分子机制。
采用逆转录-定量聚合酶链反应（RT-qPCR）分析检测组织或细胞中 circ_0109320 和 miR-595 的表达。采用 Western blot 分析检测 cleaved caspase-3、Bax、Bcl-2 和 E2F7 蛋白表达。采用 Transwell 检测评估 NSCLC 细胞系的侵袭水平。
本研究结果表明，与癌旁组织相比，NSCLC 患者肿瘤组织中 circ_0109320 的表达显著上调。上调的 circ_0109320 水平与 NSCLC 的 TNM 分期以及淋巴结转移显著相关。此外，下调 circ_0109320 水平可减弱 NSCLC 细胞的增殖和侵袭能力，同时促进细胞凋亡。我们进一步证实，circ_0109320 可通过海绵吸附 miR-595 来上调 E2F7 表达。沉默 miR-595 或过表达 E2F7 可部分逆转 circ_0109320 敲低对 NSCLC 细胞的抑制作用。这些数据表明，抑制 circ_0109320 通过 miR-595/E2F7 通路减弱 NSCLC 细胞的增殖和侵袭能力，并增强细胞凋亡。
circ_0109320/miR-595/E2F7 轴可能在 NSCLC 进展的病理机制中发挥关键作用，在 NSCLC 的未来治疗中具有潜在应用价值。
