CircRNA hsa_circ_0070659 predicts poor prognosis and promotes non-small cell lung cancer (NSCLC) progression via microRNA-377 (miR-377) / Ras-Associated Binding Protein 3C (RAB3C) pathway

CircRNA hsa_circ_0070659 通过 microRNA-377 (miR-377) / Ras 相关结合蛋白 3C (RAB3C) 通路预测不良预后并促进非小细胞肺癌 (NSCLC) 进展

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作者:Qingjun Meng, Yanguang Li, Zhen Sun, Xue Yang

Abstract

A large number of circular RNAs (circRNAs) are dysregulated in lung cancer and affect the progression and prognosis of lung disease. Herein, this study selected specific circular RNA (circ_0070659) by bioinformatics analysis and aimed to investigate the role of circ_0070659 in non-small cell lung cancer (NSCLC). The differentially expressed circRNA (hsa_circ_0070659) in NSCLC was screened from public databases (GEO), and real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to identify the circ_0070659 levels in cancer tissues and cells. NSCLC cell proliferation, migration, and invasion abilities after circ_0070659 silencing was detected by colony formation assay, Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Targeted binding between microRNA-377 (miR-377) and circ_0070659 or Ras-Associated Binding Protein 3C (RAB3C) was verified by western blot, dual-luciferase reporter assay, and RNA pull-down assay. Our experimental results showed that circ_0070659 levels were largely increased in tumor tissues and cells. Biologically, knockdown of circ_0070659 obviously inhibited proliferation, migration, and invasion of NSCLC cells. Mechanistically, circ_0070659 promoted RAB3C-mediated proliferation and invasion through sponging miR-377. Furthermore, miR-377 inhibitor reversed the inhibitory ability of circ_0070659 silencing on malignant biological behavior of NSCLC cells. Our study revealed a novel signaling pathway that circ_0070659/miR-377/RAB3C axis regulates tumor progression, and it may become a new therapeutic target for NSCLC.

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