Yao Yuanshan, Zhou Yinjie, Hua Qingwang
Department of Thoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital), Haishu District, Ningbo, Zhejiang 315010, China.
Mol Ther Nucleic Acids. 2021 Jan 5;23:783-796. doi: 10.1016/j.omtn.2020.12.031. eCollection 2021 Mar 5.
Lung adenocarcinoma (LUAD) is a subtype of lung cancer with a high incidence and mortality all over the world. In recent years, circular RNAs (circRNAs) have been verified to be a novel subtype of noncoding RNAs that exert vital functions in various cancers. Our research was designed to investigate the role of circ_0018414 in LUAD. We first observed that circ_0018414 was downregulated in LUAD tissues and cells. Also, low expression of circ_0018414 predicted unfavorable prognosis of LUAD patients. Then, upregulation of circ_0018414 repressed cell proliferation and stemness, while promoting cell apoptosis, in LUAD. Moreover, circ_0018414 overexpression enhanced the expression of its host gene, dickkopf WNT signaling pathway inhibitor 1 (DKK1), therefore inactivating the Wnt/β-catenin pathway. Additionally, circ_0018414 could sponge miR-6807-3p to protect DKK1 mRNA from miR-6807-3p-induced silencing, leading to DKK1 upregulation in LUAD cells. Finally, rescue assays proved that circ_0018414 inhibited the progression of LUAD via the miR-6807-3p/DKK1 axis-inactivated Wnt/β-catenin pathway. The findings in our work indicated circ_0018414 as a tumor inhibitor in LUAD, which might provide a new perspective for LUAD treatment.
肺腺癌（LUAD）是一种在全球范围内发病率和死亡率都很高的肺癌亚型。近年来，环状RNA（circRNAs）已被证实是一类新型的非编码RNA，在多种癌症中发挥着重要作用。我们的研究旨在探讨circ_0018414在肺腺癌中的作用。我们首先观察到circ_0018414在肺腺癌组织和细胞中表达下调。此外，circ_0018414低表达预示着肺腺癌患者预后不良。然后，在肺腺癌中上调circ_0018414可抑制细胞增殖和干性，同时促进细胞凋亡。此外，circ_0018414过表达增强了其宿主基因 dickkopf WNT信号通路抑制剂1（DKK1）的表达，从而使Wnt/β-连环蛋白通路失活。此外，circ_0018414可以吸附miR-6807-3p，保护DKK1 mRNA免受miR-6807-3p诱导的沉默，导致肺腺癌细胞中DKK1上调。最后，挽救实验证明circ_0018414通过miR-6807-3p/DKK1轴失活的Wnt/β-连环蛋白通路抑制肺腺癌的进展。我们的研究结果表明circ_0018414是肺腺癌中的一种肿瘤抑制因子，这可能为肺腺癌的治疗提供新的视角。
