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Yue Wang, Zihui Fang, Mei Hong, Da Yang, Wen Xie. Long-noncoding RNAs (lncRNAs) in drug metabolism and disposition, implications in cancer chemo-resistance[J]. Acta Pharmaceutica Sinica B, 2020, 10(1): 105-112

Long-noncoding RNAs (lncRNAs) in drug metabolism and disposition, implications in cancer chemo-resistance
Yue Wanga, Zihui Fanga,b, Mei Hongb, Da Yanga,c,d, Wen Xiea,e
a Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261, USA;
b College of Life Sciences, South China Agricultural University, Guangzhou 510642, China;
c University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA;
d Department of Computational and System Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA;
e Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA
Abstract:
Drug metabolism is an orchestrated process in which drugs are metabolized and disposed through a series of specialized enzymes and transporters. Alterations in the expression and/or activity of these enzymes and transporters can affect the bioavailability (pharmacokinetics, or PK) and therapeutic efficacy (pharmacodynamics, or PD) of drugs. Recent studies have suggested that the long non-coding RNAs (lncRNAs) are highly relevant to drug metabolism and drug resistance, including chemoresistance in cancers, through the regulation of drug metabolism and disposition related genes. This review summarizes the regulation of enzymes, transporters, or regulatory proteins involved in drug metabolism by lncRNAs, with a particular emphasis on drug metabolism and chemo-resistance in cancer patients. The perspective strategies to integrate multi-dimensional pharmacogenomics data for future in-depth analysis of drug metabolism related lncRNAs are also proposed. Understanding the role of lncRNAs in drug metabolism will not only facilitate the identification of novel regulatory mechanisms, but also enable the discovery of lncRNA-based biomarkers and drug targets to personalize and improve the therapeutic outcome of patients, including cancer patients.
Key words:    LncRNA    Drug metabolism    Chemo-resistance    Xenobiotic receptor    Regulation   
Received: 2019-06-02     Revised: 2019-08-23
DOI: 10.1016/j.apsb.2019.09.011
Funds: Our original work described in this review article was supported in part by NIH grant ES030429 (to W.X.) and CA222274 (to D.Y.). W.X. was supported in part by the Joseph Koslow Endowed Professorship from the University of Pittsburgh School of Pharmacy.
Corresponding author: Da Yang, Wen Xie     Email:dyang@pitt.edu;wex6@pitt.edu
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Yue Wang
Zihui Fang
Mei Hong
Da Yang
Wen Xie

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