Research Paper Advance Articles

Downregulation of hsa_circ_0007580 inhibits non-small cell lung cancer tumorigenesis by reducing miR-545-3p sponging

Shuifang Chen1, , Shan Lu1, , Yinan Yao1, , Junjun Chen1, , Guangdie Yang1, , Lingfang Tu1, , Zeying Zhang1, , Jianli Zhang1, , Lina Chen1, ,

  • 1 The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China

Received: January 6, 2020       Accepted: May 27, 2020       Published: July 18, 2020      

https://doi.org/10.18632/aging.103472
How to Cite

Copyright © 2020 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Non-small cell lung cancer (NSCLC) is a highly malignant tumor. Many circular RNAs (circRNAs) are reportedly in regulating the progression of NSCLC. To identify potential therapeutic targets for NSCLC, we conducted a bioinformatics analysis of circRNAs differentially expressed between NSCLC tissues and adjacent normal tissues. Hsa_circ_0007580 was upregulated in NSCLC tumor tissues, and the expression of its host gene (protein kinase Ca) correlated negatively with overall survival. Short-hairpin RNAs were used to knock down hsa_circ_0007580 in NSCLC cells, and gene and protein levels were measured with qRT-PCR and Western blotting, respectively. NSCLC cell proliferation, migration and apoptosis were evaluated with CCK-8 assays, Ki-67 staining, Transwell assays and flow cytometry, respectively. Knocking down hsa_circ_0007580 inhibited proliferation and invasion by NSCLC cells and induced their apoptosis. Dual luciferase reporter assays indicated that miR-545-3p can bind to hsa_circ_0007580 (suggesting that hsa_circ_0007580 sponges miR-545-3p) and to protein kinase Ca (suggesting that miR-545-3p directly inhibits this gene). In a xenograft tumor model, downregulating hsa_circ_0007580 inhibited NSCLC tumorigenesis by inactivating p38/mitogen-activated protein kinase signaling. Thus, silencing hsa_circ_0007580 notably inhibited NSCLC progression in vitro and in vivo, suggesting this circRNA could be a novel treatment target for NSCLC.

Abbreviations

NSCLC: non-small cell lung cancer; miRNA: microRNA; circRNA: circular RNA.