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Acute liver injury upregulates microRNA-491–5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-α-induced apoptosis

Authors

  • Sangjeong Yoon,

    1. Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA, USA
    2. Hanaro Medical Center, Yousung-gu Daejon, South Korea
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  • Tae-Hun Kim,

    1. Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA, USA
    2. Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, South Korea
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  • Arutselvan Natarajan,

    1. Department of Hematology and Oncology, University of California Davis Medical Center, Sacramento, CA, USA
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  • Si-Si Wang,

    1. Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA, USA
    2. Department of Pharmacology, Norman Bethune College of Medicine, Jilin University, Changchun, China
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  • Jeongwoo Choi,

    1. Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA, USA
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  • Jian Wu,

    1. Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA, USA
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  • Mark A. Zern,

    1. Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA, USA
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  • Senthil K. Venugopal

    1. Department of Internal Medicine: Transplant Research Program, University of California Davis Medical Center, Sacramento, CA, USA
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Correspondence
Senthil K. Venugopal, PhD, 4635 2nd Ave. Suite 1001, University of California Davis Medical Center, Sacramento, CA 95817, USA
Tel: +1 916 734 1420
Fax: +1 916 734 8097
e-mail: v_senthilk@hotmail.com

Abstract

Background: MicroRNAs (miRNAs) have emerged as novel genetic regulators of cell functions such as proliferation, apoptosis and cancer.

Aims: The aim of this study was to evaluate the role of a specific miRNA in modulating hepatic cell functions.

Methods: C57Bl/6 mice were administered anti-fas receptor antibodies to induce liver cell apoptosis. miRNAs were purified from the liver tissue and evaluated using an miRNA microarray. The role of miRNA-491_5p, which was overexpressed in the model, in modulating hepatic cell functions was evaluated. miRNA-491_5p was overexpressed in Hep G2 cells, followed by the addition of tumour necrosis factor (TNF)-α, and induction of apoptosis as well as genes involved in apoptosis pathways were evaluated. The effect of miRNA-491_5p target genes on apoptosis was also analysed by inhibiting their expression by siRNA-induced gene silencing.

Results: Upregulation of miRNA-491_5p was found in a high-dose anti-fas receptor antibody group. Overexpression of microRNA-491_5p sensitized Hep G2 cells for TNF-α-induced apoptosis, and also caused an inhibition of α-fetoprotein, (AFP), heat shock protein-90 (hsp-90) and nuclear factor-κB (NF-κB). Overexpression of miRNA-491_5p or inhibition of AFP and hsp-90 resulted in an increased apoptosis in TNF-α-treated Hep G2 cells.

Conclusions: One of the miRNAs that is associated with the acute liver injury mouse model, miRNA-491_5p, sensitizes Hep G2 cells for TNF-α-induced apoptosis, at least in part, by inhibiting AFP, hsp-90 and NF-κB.

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