Comprehensive characterization of a drug-resistance-related ceRNA network across 15 anti-cancer drug categories

Bing Liu; Xiaorui Zhou; Dongyuan Wu; Xuesong Zhang; Xiuyun Shen; Kai Mi; Zhangyi Qu; Yanan Jiang; Desi Shang

doi:10.1016/j.omtn.2021.02.011

Comprehensive characterization of a drug-resistance-related ceRNA network across 15 anti-cancer drug categories

Mol Ther Nucleic Acids. 2021 Feb 15:24:11-24. doi: 10.1016/j.omtn.2021.02.011. eCollection 2021 Jun 4.

Authors

Bing Liu^{1

2}, Xiaorui Zhou³, Dongyuan Wu⁴, Xuesong Zhang⁵, Xiuyun Shen⁶, Kai Mi⁷, Zhangyi Qu¹, Yanan Jiang^{7

2

6}, Desi Shang⁷

Affiliations

¹ Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin 150081, P.R. China.
² Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150086, P.R. China.
³ BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, P.R. China.
⁴ Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin 150030, P.R. China.
⁵ Department of Stomatology, 962 Hospital of PLA, Harbin 150080, P.R. China.
⁶ Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, P.R. China.
⁷ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, P.R. China.

Abstract

Cancer is still a major health problem around the world. The treatment failure of cancer has largely been attributed to drug resistance. Competitive endogenous RNAs (ceRNAs) are involved in various biological processes and thus influence the drug sensitivity of cancers. However, a comprehensive characterization of drug-sensitivity-related ceRNAs has not yet been performed. In the present study, we constructed 15 ceRNA networks across 15 anti-cancer drug categories, involving 217 long noncoding RNAs (lncRNAs), 158 microRNAs (miRNAs), and 1,389 protein coding genes (PCGs). We found that these ceRNAs were involved in hallmark processes such as "self-sufficiency in growth signals," "insensitivity to antigrowth signals," and so on. We then identified an intersection ceRNA network (ICN) across the 15 anti-cancer drug categories. We further identified interactions between genes in the ICN and clinically actionable genes (CAGs) by analyzing the co-expressions, protein-protein interactions, and transcription factor-target gene interactions. We found that certain genes in the ICN are correlated with CAGs. Finally, we found that genes in the ICN were aberrantly expressed in tumors, and some were associated with patient survival time and cancer stage.

Keywords: Pan-cancer; ceRNA network; drug resistance; lncRNA.