lncRNA CCAT1 Acts as a MicroRNA-218 Sponge to Increase Gefitinib Resistance in NSCLC by Targeting HOXA1

Xiang Jin; Xiuhua Liu; Zhen Zhang; Yinghui Guan

doi:10.1016/j.omtn.2020.01.006

lncRNA CCAT1 Acts as a MicroRNA-218 Sponge to Increase Gefitinib Resistance in NSCLC by Targeting HOXA1

Mol Ther Nucleic Acids. 2020 Mar 6:19:1266-1275. doi: 10.1016/j.omtn.2020.01.006. Epub 2020 Jan 17.

Authors

Xiang Jin¹, Xiuhua Liu¹, Zhen Zhang², Yinghui Guan³

Affiliations

¹ Department of Respiration, The First Hospital of Jilin University, Changchun 130021, China.
² PICU, The First Hospital of Jilin University, Changchun 130021, China.
³ Department of Respiration, The First Hospital of Jilin University, Changchun 130021, China. Electronic address: xuejun1610@163.com.

Abstract

Long non-coding RNA (lncRNA) colon cancer-associated transcript-1 (CCAT1) has been reported to play important roles in the development and progression of multiple human malignancies. However, the functional role and molecular mechanism of CCAT1 on gefitinib resistance in non-small cell lung cancer (NSCLC) are largely unclear. The aim of this study is to explore the roles of CCAT1 on gefitinib resistance in NSCLC and to explore the underlying mechanisms. The quantitative real-time PCR (qRT-PCR) analysis was to investigate the expression pattern of CCAT1 in gefitinib-resistant NSCLC patient tissues and cell lines, and then the effects of CCAT1 on gefitinib resistance of NSCLC in vitro and in vivo. Furthermore, bioinformatics online program predictions and luciferase reporter assay were used to validate the association of CCAT1 and miR-218 in NSCLC cells. In this study, CCAT1 was observed to be upregulated in gefitinib-resistant patient tissues and cell lines. In vitro and in vivo experiments demonstrated that CCAT1 knockdown impaired cell proliferation and promoted the gefitinib-induced cell apoptosis. Furthermore, we demonstrated that CCAT1 acts as a sponge for miR-218, and verified that HOXA1 is a novel target of miR-218. These results suggest that CCAT1 may serve as a promising therapeutic target for the treatment of epidermal growth factor receptor (EGFR) plus NSCLC patients.

Keywords: CCAT1; NSCLC; ceRNA; gefitinib; lncRNA.