LncRNA HNF1A-AS1 替代转录本的鉴定和功能表征及其对细胞生长、分化、肝脏疾病和药物诱导的影响。

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2024-04-21 DOI:10.3390/ncrna10020028
Jing Jin, Le Tra Giang Nguyen, Andrew Wassef, Ragui Sadek, Timothy M Schmitt, Grace L Guo, Theodore P Rasmussen, Xiao-Bo Zhong
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引用次数: 0

摘要

长非编码 RNA(lncRNA)肝细胞核因子-1α(HNF1A)反义 RNA 1(HNF1A-AS1)是肝脏生长、发育、细胞分化和药物代谢的重要 lncRNA。与许多 lncRNA 一样,HNF1A-AS1 在人类基因组中有多个注释替代转录本。几个基本的生物学问题仍未解决:(1) 在肝脏样本和肝细胞系等生物样本中到底存在多少转录本? (2) 在不同条件下,包括在细胞生长和发育过程中、暴露于异生物体(如药物)后,以及在代谢功能障碍相关性脂肪性肝病(MASLD)、酒精相关性肝病(ALD)肝硬化和肥胖症等疾病条件下,不同的 HNF1A-AS1 替代转录本的表达模式是什么?(3) 先前研究中使用的 siRNA 是否会敲除一个或多个转录本?(4) 不同的转录本是否具有相同或不同的基因调控功能?所提供的数据证实了肝脏样本和细胞系中存在几种已注释的 HNF1A-AS1 转录本,同时也发现了一些 Ensembl 基因组数据库中未注释的新转录本。已发现的 HNF1A-AS1 转录本的表达模式与人类胚胎干细胞(hESC)成熟肝细胞样细胞的细胞分化、HepaRG 细胞的生长和分化、利福平诱导反应以及各种肝病状况高度相关。在 HepaRG 生长、分化和对利福平诱导的反应过程中,HNF1A-AS1 转录物的表达水平与细胞色素 P450 酶(如 CYP3A4)的表达水平也高度相关。
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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.

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.

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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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