Acute liver injury upregulates microRNA-491–5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-α-induced apoptosis
Version of Record online: 14 DEC 2009
© 2009 John Wiley & Sons A/S
Volume 30, Issue 3, pages 376–387, March 2010
How to Cite
Yoon, S., Kim, T.-H., Natarajan, A., Wang, S.-S., Choi, J., Wu, J., Zern, M. A. and Venugopal, S. K. (2010), Acute liver injury upregulates microRNA-491–5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-α-induced apoptosis. Liver International, 30: 376–387. doi: 10.1111/j.1478-3231.2009.02181.x
- Issue online: 18 JAN 2010
- Version of Record online: 14 DEC 2009
- Received 22 January 2009Accepted 8 November 2009
- heat shock protein-90;
- liver injury;
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.