Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer

Xiangzhen Kong; Shousen Hu; Yongliang Yuan; Yue Du; Zijia Zhu; Zhizhen Song; Shanshan Lu; Chang Zhao; Dan Yan

doi:10.7150/jca.40729

Analysis of lncRNA, miRNA and mRNA-associated ceRNA networks and identification of potential drug targets for drug-resistant non-small cell lung cancer

J Cancer. 2020 Mar 5;11(11):3357-3368. doi: 10.7150/jca.40729. eCollection 2020.

Authors

Xiangzhen Kong^{1

2}, Shousen Hu³, Yongliang Yuan^{1

2}, Yue Du^{1

2}, Zijia Zhu^{1

2}, Zhizhen Song^{1

2}, Shanshan Lu^{1

2}, Chang Zhao³, Dan Yan^{1

2}

Affiliations

¹ Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China.
³ Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Background: Drug resistance to chemotherapeutic drugs or targeted medicines is an obstacle encountered in the treatment of non-small-cell lung cancer (NSCLC). However, the mechanisms of competing endogenous RNA (ceRNA) on the drug resistance in NSCLC are rarely reported. In this paper, the comprehensive expression profiles of lncRNAs and mRNAs in drug-resistant NSCLC cells were obtained by RNA sequencing. Methods: The dysregulated lncRNAs, miRNAs and mRNAs in drug-resistant NSCLC cell lines were identified by RNA-sequencing and bioinformatics methods. Results: A total of 39 dysregulated lncRNAs and 650 dysregulated mRNAs were identified between drug-resistant NSCLC cell lines and their parental cell lines. Additionally, 33 lncRNA-miRNA-mRNA pathways in the ceRNA network in drug-resistant NSCLC were constructed through bioinformatics methods and ceRNA regulatory rules. These comprised 12 dysregulated lncRNAs, five dysregulated miRNAs, and eight dysregulated mRNAs. In addition, lncRNA ATP2B1/miR-222-5p/TAB2 and lncRNA HUWE1/miR-222-5p/TAB2 were identified as potential ceRNA networks involved in drug resistance to NSCLC. Conclusions: The current study provides a promising therapeutic strategy against the lncRNA-miRNA-mRNA ceRNA regulatory network for NSCLC treatment and deepens our comprehension of the ceRNA regulatory mechanisms related to drug resistance to NSCLC.

Keywords: RNA sequencing; competing endogenous RNA network; drug resistance; non-small cell lung cancer.