a Department of Otolaryngology , The 2nd Clinical Medicine College (Shenzhen People's Hospital) of Jinan University , Shenzhen , China.
b Interated Chinese and Western Medicine Postdoctoral research station , Jinan University , Guangzhou , China.
Cell Cycle. 2018;17(16):2080-2090. doi: 10.1080/15384101.2018.1515553. Epub 2018 Sep 13.
Circular RNA (circRNA) is shown to participate in various tumors, including lung cancer. Although a few circRNAs involved in lung cancer are reported, whether circRNA negatively regulates lung cancer development remains elusive. In this study, we showed hsa_circ_100395 expression was decreased in lung cancer tissues. Besides, hsa_circ_100395 level was inversely correlated with TNM stage and metastases in lung cancer and low hsa_circ_100395 expression in patients predicted poor prognosis. Overexpression of hsa_circ_100395 dramatically inhibited lung cancer cell proliferation, arrested cell-cycle progression and reduced cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_100395 overexpression delayed tumor growth in vivo. Mechanistically, we showed hsa_circ_100395 serves as a sponge for miR-1228 targeting TCF21 in lung cancer. Rescue assays indicated that hsa_circ_100395 regulates lung cancer cell proliferation, migration and invasion through modulating miR-1228/TCF21 pathway. Altogether, our study reveals a novel regulatory loop that hsa_circ_100395/miR-1228/TCF21 axis modulates lung cancer development.
circRNA: circular RNA; miRNA: microRNA; RNA-FISH: RNA fluorescence in situy bridization; qRT-PCR: Reverse transcription and quantitative real-time PCR.
环状 RNA(circRNA)被证明参与多种肿瘤,包括肺癌。尽管已有一些涉及肺癌的 circRNA 被报道,但 circRNA 是否负调控肺癌的发展仍不清楚。在本研究中,我们显示 hsa_circ_100395 在肺癌组织中的表达降低。此外,hsa_circ_100395 水平与肺癌的 TNM 分期和转移呈负相关,患者的低 hsa_circ_100395 表达预示着预后不良。hsa_circ_100395 的过表达显著抑制肺癌细胞的增殖,体外细胞周期进程停滞,并降低细胞迁移和侵袭。异种移植实验表明,hsa_circ_100395 的过表达在体内延缓了肿瘤的生长。从机制上讲,我们表明 hsa_circ_100395 作为 microRNA-1228 靶向 TCF21 的海绵在肺癌中发挥作用。挽救实验表明,hsa_circ_100395 通过调节 miR-1228/TCF21 通路调节肺癌细胞的增殖、迁移和侵袭。总之,我们的研究揭示了一个新的调控环,即 hsa_circ_100395/miR-1228/TCF21 轴调节肺癌的发展。
circRNA:环状 RNA;miRNA:microRNA;RNA-FISH:RNA 荧光原位杂交;qRT-PCR:逆转录和定量实时 PCR。