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ncRNA
Special Issues
Roles of Non-coding RNAs in Drug Metabolism and Disposition
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Roles of Non-coding RNAs in Drug Metabolism and Disposition

A special issue of Non-Coding RNA (ISSN 2311-553X). This special issue belongs to the section "Long Non-Coding RNA".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 3562

Special Issue Editors

Prof. Dr. Xiaobo Zhong

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, 69 N Eagleville Road, Storrs, CT 06269, USA
Interests: P450-mediated drug metabolism; drug-induced liver injury; epigenetics; lncRNAs; nucleic acid therapeutics; ASOs; siRNAs
Prof. Dr. Lirong Zhang

E-Mail Website
Guest Editor
Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
Interests: epigenetics; non-coding RNAs; nuclear receptors; ontogeny of drug-metabolizing enzymes

Special Issue Information

Dear Colleagues,

Drug metabolism and disposition are biological processes that occur after drugs are administrated into the body, including absorption, distribution, metabolism, and excretion (ADME), which have direct impacts on the therapeutic efficacy and toxicity of drugs. Drug-metabolizing enzymes and transporters are major key players in determining the features of ADME of small chemical drugs, which are tightly regulated by various key regulatory factors, including non-coding RNAs (ncRNAs). Accumulated evidence has shown that microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) participate in regulatory events at various levels of transcription, post-transcription, and translation to control expression of drug-metabolizing enzymes and transporters at the key drug-processing organs, such as the liver, intestine, and kidneys. This Special Issue aims to publish a set of research and review articles focusing on the emerging knowledge of the roles of ncRNAs in drug metabolism and disposition.

Prof. Dr. Xiaobo Zhong
Prof. Dr. Lirong Zhang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Non-Coding RNA is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ncRNAs
  • lncRNAs
  • miRNAs
  • drug metabolizing enzymes
  • transporters

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Published Papers (2 papers)

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Research

18 pages, 5770 KiB  
Article
An Integrative Transcriptome Subtraction Strategy to Identify Human lncRNAs That Specifically Play a Role in Activation of Human Hepatic Stellate Cells
by Yonghe Ma, Jamie Harris, Ping Li, Chengfei Jiang, Hang Sun and Haiming Cao
Non-Coding RNA 2024, 10(3), 34; https://doi.org/10.3390/ncrna10030034 - 6 Jun 2024
Viewed by 1128
Abstract
Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from “activated” hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to [...] Read more.
Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from “activated” hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to define the role of human long non-coding RNAs (lncRNAs) in hHSC activation. To address this challenge, we identified another cell type that acts via a diverse gene network to promote fibrogenesis. Then, we identified the lncRNAs that were differentially regulated in activated hHSCs and the other profibrotic cell. Next, we conducted concurrent analysis to identify those lncRNAs that were specifically involved in fibrogenesis. We tested and confirmed that transdifferentiation of vascular smooth muscle cells (VSMCs) represents such a process. By overlapping TGFβ-regulated lncRNAs in multiple sets of hHSCs and VSMCs, we identified a highly selected list of lncRNA candidates that could specifically play a role in hHSC activation. We experimentally characterized one human lncRNA, named CARMN, which was significantly regulated by TGFβ in all conditions above. CARMN knockdown significantly reduced the expression levels of a panel of marker genes for hHSC activation, as well as the levels of ECM deposition and hHSC migration. Conversely, gain of function of CARMN using CRISPR activation (CRISPR-a) yielded the completely opposite effects. Taken together, our work addresses a bottleneck in identifying human lncRNAs that specifically play a role in hHSC activation and provides a framework to effectively select human lncRNAs with significant pathophysiological role. Full article
(This article belongs to the Special Issue Roles of Non-coding RNAs in Drug Metabolism and Disposition)
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18 pages, 4384 KiB  
Article
Identification and Functional Characterization of Alternative Transcripts of LncRNA HNF1A-AS1 and Their Impacts on Cell Growth, Differentiation, Liver Diseases, and in Response to Drug Induction
by Jing Jin, Le Tra Giang Nguyen, Andrew Wassef, Ragui Sadek, Timothy M. Schmitt, Grace L. Guo, Theodore P. Rasmussen and Xiao-bo Zhong
Non-Coding RNA 2024, 10(2), 28; https://doi.org/10.3390/ncrna10020028 - 21 Apr 2024
Viewed by 1659
Abstract
The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological [...] Read more.
The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database. Expression patterns of the identified HNF1A-AS1 transcripts are highly correlated with the cell differentiation of matured hepatocyte-like cells from human embryonic stem cells (hESC), growth and differentiation of HepaRG cells, in response to rifampicin induction, and in various liver disease conditions. The expression levels of the HNF1A-AS1 transcripts are also highly correlated to the expression of cytochrome P450 enzymes, such as CYP3A4, during HepaRG growth, differentiation, and in response to rifampicin induction. Full article
(This article belongs to the Special Issue Roles of Non-coding RNAs in Drug Metabolism and Disposition)
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