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

Sangjeong Yoon, Tae Hun Kim, Arutselvan Natarajan, Si Si Wang, Jeongwoo Choi, Jian Wu, Mark A Zern, Senthil K. Venugopal

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)376-387
Number of pages12
JournalLiver International
Volume30
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Hep G2 Cells
MicroRNAs
Up-Regulation
Tumor Necrosis Factor-alpha
Apoptosis
Liver
Wounds and Injuries
Fetal Proteins
HSP90 Heat-Shock Proteins
CD95 Antigens
Hepatocytes
Antibodies
Gene Silencing
Small Interfering RNA
Genes

Keywords

  • α-fetoprotein
  • Apoptosis
  • Heat shock protein-90
  • Hepatocytes
  • Liver injury
  • MicroRNA

ASJC Scopus subject areas

  • Hepatology

Cite this

Acute liver injury upregulates microRNA-491-5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-α-induced apoptosis. / Yoon, Sangjeong; Kim, Tae Hun; Natarajan, Arutselvan; Wang, Si Si; Choi, Jeongwoo; Wu, Jian; Zern, Mark A; Venugopal, Senthil K.

In: Liver International, Vol. 30, No. 3, 03.2010, p. 376-387.

Research output: Contribution to journalArticle

Yoon, Sangjeong ; Kim, Tae Hun ; Natarajan, Arutselvan ; Wang, Si Si ; Choi, Jeongwoo ; Wu, Jian ; Zern, Mark A ; Venugopal, Senthil K. / Acute liver injury upregulates microRNA-491-5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-α-induced apoptosis. In: Liver International. 2010 ; Vol. 30, No. 3. pp. 376-387.
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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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T1 - Acute liver injury upregulates microRNA-491-5p in mice, and its overexpression sensitizes Hep G2 cells for tumour necrosis factor-α-induced apoptosis

AU - Yoon, Sangjeong

AU - Kim, Tae Hun

AU - Natarajan, Arutselvan

AU - Wang, Si Si

AU - Choi, Jeongwoo

AU - Wu, Jian

AU - Zern, Mark A

AU - Venugopal, Senthil K.

PY - 2010/3

Y1 - 2010/3

N2 - 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.

AB - 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.

KW - α-fetoprotein

KW - Apoptosis

KW - Heat shock protein-90

KW - Hepatocytes

KW - Liver injury

KW - MicroRNA

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U2 - 10.1111/j.1478-3231.2009.02181.x

DO - 10.1111/j.1478-3231.2009.02181.x

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C2 - 20015148

AN - SCOPUS:77950619689

VL - 30

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JO - Liver International

JF - Liver International

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