PMID- 38176619
OWN - NLM
STAT- MEDLINE
DCOM- 20240202
LR  - 20240206
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 220
DP  - 2024 Feb
TI  - The long noncoding RNA HNF1A-AS1 with dual functions in the regulation of 
      cytochrome P450 3A4.
PG  - 116016
LID - S0006-2952(23)00609-3 [pii]
LID - 10.1016/j.bcp.2023.116016 [doi]
AB  - Cytochrome P450 3A4 (CYP3A4) is the most important and abundant drug-metabolizing 
      enzyme in the human liver. Inter-individual differences in the expression and 
      activity of CYP3A4 affect clinical and precision medicine. Increasing evidence 
      indicates that long noncoding RNAs (lncRNAs) play crucial roles in the regulation 
      of CYP3A4 expression. Here, we showed that lncRNA hepatocyte nuclear factor 1 
      alpha-antisense 1 (HNF1A-AS1) exerted dual functions in regulating CYP3A4 
      expression in Huh7 and HepG2 cells. Mechanistically, HNF1A-AS1 served as an RNA 
      scaffold to interact with both protein arginine methyltransferase 1 and 
      pregnane X receptor (PXR), thereby facilitating their protein interactions and 
      resulting in the transactivation of PXR and transcriptional alteration of CYP3A4 
      via histone modifications. Furthermore, HNF1A-AS1 bound to the HNF1A protein, a 
      liver-specific transcription factor, thereby blocking its interaction with the E3 
      ubiquitin ligase tripartite motif containing 25, ultimately preventing HNF1A 
      ubiquitination and protein degradation, further regulating the expression of 
      CYP3A4. In summary, these results reveal the novel functions of HNF1A-AS1 as the 
      transcriptional and post-translational regulator of CYP3A4; thus, HNF1A-AS1 may 
      serve as a new indicator for establishing or predicting individual differences in 
      CYP3A4 expression.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Wang, Yiting
AU  - Wang Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical 
      Science, Zhengzhou University, Zhengzhou, 450001 Zhengzhou, China; Department of 
      Clinical Pharmacology, School of Medicine, Henan University of Chinese Medicine, 
      450046 Zhengzhou, China.
FAU - Wang, Pei
AU  - Wang P
AD  - Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical 
      Science, Zhengzhou University, Zhengzhou, 450001 Zhengzhou, China.
FAU - Wang, Qi
AU  - Wang Q
AD  - Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical 
      Science, Zhengzhou University, Zhengzhou, 450001 Zhengzhou, China.
FAU - Chen, Shitong
AU  - Chen S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical 
      Science, Zhengzhou University, Zhengzhou, 450001 Zhengzhou, China.
FAU - Wang, Xiaofei
AU  - Wang X
AD  - Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical 
      Science, Zhengzhou University, Zhengzhou, 450001 Zhengzhou, China.
FAU - Zhong, Xiaobo
AU  - Zhong X
AD  - Department of Pharmaceutical Sciences, School of Pharmacy, University of 
      Connecticut, 06269 Storrs, CT, USA.
FAU - Hu, Wanglai
AU  - Hu W
AD  - Translational Research Institute, Zhengzhou University People's Hospital, Academy 
      of Medical Science, Zhengzhou University, 450003 Zhengzhou, China.
FAU - Thorne, Rick F
AU  - Thorne RF
AD  - Translational Research Institute, Zhengzhou University People's Hospital, Academy 
      of Medical Science, Zhengzhou University, 450003 Zhengzhou, China.
FAU - Han, Shengna
AU  - Han S
AD  - Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical 
      Science, Zhengzhou University, Zhengzhou, 450001 Zhengzhou, China. Electronic 
      address: hsn@zzu.edu.cn.
FAU - Wu, Mian
AU  - Wu M
AD  - Translational Research Institute, Zhengzhou University People's Hospital, Academy 
      of Medical Science, Zhengzhou University, 450003 Zhengzhou, China. Electronic 
      address: wumian@ustc.edu.cn.
FAU - Zhang, Lirong
AU  - Zhang L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical 
      Science, Zhengzhou University, Zhengzhou, 450001 Zhengzhou, China. Electronic 
      address: lrzhang@zzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240102
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 1.14.14.55 (CYP3A4 protein, human)
RN  - 0 (long non-coding RNA HNF1A-AS1, human)
SB  - IM
MH  - Humans
MH  - Cytochrome P-450 CYP3A/genetics
MH  - Gene Expression Regulation
MH  - Hepatocyte Nuclear Factor 1-alpha/genetics
MH  - Liver
MH  - *RNA, Long Noncoding/genetics
OTO - NOTNLM
OT  - CYP3A4
OT  - PRMT1
OT  - Post-translational regulation
OT  - TRIM25
OT  - Transcriptional regulation
OT  - lncRNA HNF1A-AS1
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2024/01/05 00:42
MHDA- 2024/01/29 06:43
CRDT- 2024/01/04 19:15
PHST- 2023/10/25 00:00 [received]
PHST- 2023/12/21 00:00 [revised]
PHST- 2023/12/28 00:00 [accepted]
PHST- 2024/01/29 06:43 [medline]
PHST- 2024/01/05 00:42 [pubmed]
PHST- 2024/01/04 19:15 [entrez]
AID - S0006-2952(23)00609-3 [pii]
AID - 10.1016/j.bcp.2023.116016 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2024 Feb;220:116016. doi: 10.1016/j.bcp.2023.116016. Epub 2024 
      Jan 2.