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Mir-34a is upregulated during liver regeneration in rats and is associated with the suppression of hepatocyte proliferation.

Chen H, Sun Y, Dong R, Yang S, Pan C, Xiang D, Miao M, Jiao B - PLoS ONE (2011)

Bottom Line: In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay.A decrease of INHBB and Met was detected in regenerating liver.MiR-34a expression was upregulated during the late phase of liver regeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.

ABSTRACT

Background: MicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism and proliferation. This study aims to explore the effect of miR-34a in hepatocyte proliferation and its potential role in liver regeneration termination.

Methodology/principal finding: MiR-34a was highly induced after partial hepatectomy. Overexpression of miR-34a in BRL-3A cells could significantly inhibit cell proliferation and down-regulate the expression of inhibin βB (INHBB) and Met. In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay. More importantly, INHBB siRNA significantly repressed cell proliferation. A decrease of INHBB and Met was detected in regenerating liver.

Conclusion/significance: MiR-34a expression was upregulated during the late phase of liver regeneration. MiR-34a-mediated regulation of INHBB and Met may collectively contribute to the suppression of hepatocyte proliferation.

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Related in: MedlinePlus

Expression of INHBB and Met in regenerating livers.(A) mRNA expression of INHBB and Met in regenerating liver at 5 d after resection by qRT-PCR. (B) Protein expression of INHBB and Met in regenerating liver at 5 d by westernblot analysis. Actin was used as sample control. (C) Expressive patterns of INHBB and INHBA mRNA in the regenerating liver after PHx by qRT-PCR. (D) The activin protein complexes are composed of inhibin beta A (INHBA) and inhibin beta B (INHBB) subunits.
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pone-0020238-g005: Expression of INHBB and Met in regenerating livers.(A) mRNA expression of INHBB and Met in regenerating liver at 5 d after resection by qRT-PCR. (B) Protein expression of INHBB and Met in regenerating liver at 5 d by westernblot analysis. Actin was used as sample control. (C) Expressive patterns of INHBB and INHBA mRNA in the regenerating liver after PHx by qRT-PCR. (D) The activin protein complexes are composed of inhibin beta A (INHBA) and inhibin beta B (INHBB) subunits.

Mentions: To determine whether miR-34a potentially regulates the expression of INHBB and Met during LR, we tested the expression of INHBB and Met in regenerating liver tissues at 5 d after PHx, when miR-34a was highly induced. By qRT-PCR and westernblot analysis, we observed intensive down-regulation of INHBB and Met on both mRNA and protein levels in PHx rats, indicating that miR-34a and its two candidate target genes were inversely expressed (Figure 5A,B). Moreover, we found that after PHx INHBB mRNA had declined at 3 d, and was markedly repressed at 5 d and 7 d; while INHBA mRNA had increased at 3 d, and then was strongly increased at 5 d and 7 d (Figure 5C). Our data indicated that activin B (homodimer of two INHBB proteins) had an opposite expression pattern as compared to activin A (homodimer of two INHBA proteins) (Figure 5D).


Mir-34a is upregulated during liver regeneration in rats and is associated with the suppression of hepatocyte proliferation.

Chen H, Sun Y, Dong R, Yang S, Pan C, Xiang D, Miao M, Jiao B - PLoS ONE (2011)

Expression of INHBB and Met in regenerating livers.(A) mRNA expression of INHBB and Met in regenerating liver at 5 d after resection by qRT-PCR. (B) Protein expression of INHBB and Met in regenerating liver at 5 d by westernblot analysis. Actin was used as sample control. (C) Expressive patterns of INHBB and INHBA mRNA in the regenerating liver after PHx by qRT-PCR. (D) The activin protein complexes are composed of inhibin beta A (INHBA) and inhibin beta B (INHBB) subunits.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105003&req=5

pone-0020238-g005: Expression of INHBB and Met in regenerating livers.(A) mRNA expression of INHBB and Met in regenerating liver at 5 d after resection by qRT-PCR. (B) Protein expression of INHBB and Met in regenerating liver at 5 d by westernblot analysis. Actin was used as sample control. (C) Expressive patterns of INHBB and INHBA mRNA in the regenerating liver after PHx by qRT-PCR. (D) The activin protein complexes are composed of inhibin beta A (INHBA) and inhibin beta B (INHBB) subunits.
Mentions: To determine whether miR-34a potentially regulates the expression of INHBB and Met during LR, we tested the expression of INHBB and Met in regenerating liver tissues at 5 d after PHx, when miR-34a was highly induced. By qRT-PCR and westernblot analysis, we observed intensive down-regulation of INHBB and Met on both mRNA and protein levels in PHx rats, indicating that miR-34a and its two candidate target genes were inversely expressed (Figure 5A,B). Moreover, we found that after PHx INHBB mRNA had declined at 3 d, and was markedly repressed at 5 d and 7 d; while INHBA mRNA had increased at 3 d, and then was strongly increased at 5 d and 7 d (Figure 5C). Our data indicated that activin B (homodimer of two INHBB proteins) had an opposite expression pattern as compared to activin A (homodimer of two INHBA proteins) (Figure 5D).

Bottom Line: In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay.A decrease of INHBB and Met was detected in regenerating liver.MiR-34a expression was upregulated during the late phase of liver regeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China.

ABSTRACT

Background: MicroRNAs are a class of small regulatory RNAs that modulate a variety of biological processes, including cellular differentiation, apoptosis, metabolism and proliferation. This study aims to explore the effect of miR-34a in hepatocyte proliferation and its potential role in liver regeneration termination.

Methodology/principal finding: MiR-34a was highly induced after partial hepatectomy. Overexpression of miR-34a in BRL-3A cells could significantly inhibit cell proliferation and down-regulate the expression of inhibin βB (INHBB) and Met. In BRL-3A cells, INHBB was identified as a direct target of miR-34a by luciferase reporter assay. More importantly, INHBB siRNA significantly repressed cell proliferation. A decrease of INHBB and Met was detected in regenerating liver.

Conclusion/significance: MiR-34a expression was upregulated during the late phase of liver regeneration. MiR-34a-mediated regulation of INHBB and Met may collectively contribute to the suppression of hepatocyte proliferation.

Show MeSH
Related in: MedlinePlus