Long-noncoding RNAs (lncRNAs) in drug metabolism and disposition, implications in cancer chemo-resistance.,Acta Pharmaceutica Sinica B

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Long-noncoding RNAs (lncRNAs) in drug metabolism and disposition, implications in cancer chemo-resistance.
Acta Pharmaceutica Sinica B ( IF 14.7 ) Pub Date : 2019-10-19 , DOI: 10.1016/j.apsb.2019.09.011
Yue Wang ₁ , Zihui Fang _{1,

2} , Mei Hong ₂ , Da Yang _{1,

3,

4} , Wen Xie _{1,

5}

Affiliation

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 chemo-resistance 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.

中文翻译：

药物代谢和处置中的长非编码RNA（lncRNA），对癌症的化学耐药性有影响。

药物代谢是精心策划的过程，其中药物通过一系列专门的酶和转运蛋白进行代谢和处置。这些酶和转运蛋白的表达和/或活性改变会影响药物的生物利用度（药代动力学或PK）和治疗功效（药效学或PD）。最近的研究表明，长的非编码RNA（lncRNA）通过调节药物代谢和与处置相关的基因，与药物代谢和药物耐药性（包括癌症的化学耐药性）高度相关。这篇综述总结了lncRNAs参与药物代谢的酶，转运蛋白或调节蛋白的调控，特别着重于癌症患者的药物代谢和抗化学性。还提出了整合多维药物基因组学数据以用于未来与药物代谢相关的lncRNA的深入分析的透视策略。理解lncRNA在药物代谢中的作用不仅将有助于鉴定新的调节机制，而且还使得能够发现基于lncRNA的生物标记物和药物靶标，从而个性化和改善包括癌症患者在内的患者的治疗结果。

更新日期：2019-10-19

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