Bioinformatic analysis of microRNA networks following the activation of the constitutive androstane receptor (CAR) in mouse liver

Ruixin Hao, Shengzhong Su, Yinan Wan, Frank Shen, Ben Niu, Denise M. Coslo, Istvan Albert, Xing Han, Curtis John Omiecinski

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The constitutive androstane receptor (CAR; NR1I3) is a member of the nuclear receptor superfamily that functions as a xenosensor, serving to regulate xenobiotic detoxification, lipid homeostasis and energy metabolism. CAR activation is also a key contributor to the development of chemical hepatocarcinogenesis in mice. The underlying pathways affected by CAR in these processes are complex and not fully elucidated. MicroRNAs (miRNAs) have emerged as critical modulators of gene expression and appear to impact many cellular pathways, including those involved in chemical detoxification and liver tumor development. In this study, we used deep sequencing approaches with an Illumina HiSeq platform to differentially profile microRNA expression patterns in livers from wild type C57BL/6J mice following CAR activation with the mouse CAR-specific ligand activator, 1,4-bis-[2-(3,5,-dichloropyridyloxy)] benzene (TCPOBOP). Bioinformatic analyses and pathway evaluations were performed leading to the identification of 51 miRNAs whose expression levels were significantly altered by TCPOBOP treatment, including mmu-miR-802-5p and miR-485-3p. Ingenuity Pathway Analysis of the differentially expressed microRNAs revealed altered effector pathways, including those involved in liver cell growth and proliferation. A functional network among CAR targeted genes and the affected microRNAs was constructed to illustrate how CAR modulation of microRNA expression may potentially mediate its biological role in mouse hepatocyte proliferation. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

Original languageEnglish (US)
Pages (from-to)1228-1237
Number of pages10
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1859
Issue number9
DOIs
StatePublished - Sep 1 2016

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Bioinformatics
Computational Biology
MicroRNAs
Liver
Chemical activation
Detoxification
Xenobiotics
Cytoplasmic and Nuclear Receptors
High-Throughput Nucleotide Sequencing
constitutive androstane receptor
Cell proliferation
Cell growth
Inbred C57BL Mouse
Lipid Metabolism
Gene expression
Energy Metabolism
Modulators
Tumors
Hepatocytes
Homeostasis

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Hao, Ruixin ; Su, Shengzhong ; Wan, Yinan ; Shen, Frank ; Niu, Ben ; Coslo, Denise M. ; Albert, Istvan ; Han, Xing ; Omiecinski, Curtis John. / Bioinformatic analysis of microRNA networks following the activation of the constitutive androstane receptor (CAR) in mouse liver. In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms. 2016 ; Vol. 1859, No. 9. pp. 1228-1237.
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Bioinformatic analysis of microRNA networks following the activation of the constitutive androstane receptor (CAR) in mouse liver. / Hao, Ruixin; Su, Shengzhong; Wan, Yinan; Shen, Frank; Niu, Ben; Coslo, Denise M.; Albert, Istvan; Han, Xing; Omiecinski, Curtis John.

In: Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, Vol. 1859, No. 9, 01.09.2016, p. 1228-1237.

Research output: Contribution to journalArticle

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AU - Hao, Ruixin

AU - Su, Shengzhong

AU - Wan, Yinan

AU - Shen, Frank

AU - Niu, Ben

AU - Coslo, Denise M.

AU - Albert, Istvan

AU - Han, Xing

AU - Omiecinski, Curtis John

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