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人源环状RNA hsa_circ_0001666通过miR-1184/miR-548I/AGO1轴促进非小细胞肺癌的迁移和侵袭。

Hsa_circ_0001666 promotes non-small cell lung cancer migration and invasion through miR-1184/miR-548I/AGO1 axis.

作者信息

Wang Xueting, Li Rui, Feng Lingxin, Wang Jing, Qi Qi, Wei Wenjie, Yu Zhuang

机构信息

Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266000, China.

Health Management Center, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266000, China.

出版信息

Mol Ther Oncolytics. 2022 Feb 15;24:597-611. doi: 10.1016/j.omto.2022.02.011. eCollection 2022 Mar 17.

Abstract

Accumulating evidence has revealed that the dysregulation of circular RNAs (circRNAs) plays crucial roles in the occurrence and progression of cancers. However, the aberrant expression profile and dysfunction of circRNAs in non-small cell lung cancer (NSCLC) have not been fully explored. Herein, we discovered that a circRNA, hsa_circ_0001666 (circ0001666), was highly expressed in NSCLC tissues and cell lines, and it was positively correlated with NSCLC tumor pathological grade and lymph node metastasis. Moreover, Kaplan-Meier survival analysis implied that NSCLC patients with high circ0001666 expression were negatively correlated with favorable survival. Functionally, circ0001666 could promote migration and invasion of NSCLC cells and . Mechanistically, circ0001666 could act as a sponge to miR-1184/miR-548I and upregulate the expression of AGO1, thereby promoting the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway in NSCLC cells. Collectively, these findings demonstrated that circ0001666 could serve as an oncogene to promote the migration and invasion of NSCLC via a novel miR-1184/miR-548I/AGO1 axis, which might be a promising therapeutic target for NSCLC treatment.

摘要

越来越多的证据表明,环状RNA(circRNA)的失调在癌症的发生和发展中起着关键作用。然而,circRNA在非小细胞肺癌(NSCLC)中的异常表达谱和功能障碍尚未得到充分研究。在此,我们发现一种circRNA,hsa_circ_0001666(circ0001666),在NSCLC组织和细胞系中高表达,并且与NSCLC肿瘤病理分级和淋巴结转移呈正相关。此外,Kaplan-Meier生存分析表明,circ0001666高表达的NSCLC患者的生存与良好预后呈负相关。在功能上,circ0001666可以促进NSCLC细胞的迁移和侵袭。机制上,circ0001666可以作为miR-1184/miR-548I的海绵,上调AGO1的表达,从而促进NSCLC细胞中磷脂酰肌醇3激酶(PI3K)/AKT/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的激活。总的来说,这些发现表明circ0001666可以作为一种癌基因,通过一种新的miR-1184/miR-548I/AGO1轴促进NSCLC的迁移和侵袭,这可能是NSCLC治疗的一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06f3/8892028/8fa8ea14b672/fx1.jpg

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