Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide MicroRNA Downregulation as a Negative Feedback Mechanism in the Early Phases of Liver Regeneration

ABSTRACT: Liver is one of the few organs that have the capacity to regenerate in response to injury. We carried out genome-wide miRNA microarray studies during liver regeneration in rats after 70% partial hepatectomy (PH) at early and mid-time points to more thoroughly understand their role. At 3, 12 and 18 hrs post-PH ~ 40% of the miRNAs tested were up-regulated. Conversely, at 24 hrs post-PH, ~ 70% of miRNAs were down-regulated. Further, we established that the genome-wide down-regulation of miRNA expression at 24 hrs was also correlated with decreased expression of genes such as Rnasen, Dgcr8, Dicer, Tarbp2 and Prkra that are associated with miRNA biogenesis. To determine if a potential negative feedback loop between miRNAs and their regulatory genes existed, 11 candidate miRNAs which were predicted to target the above genes were examined and found to be up-regulated at 3 hrs post-PH. Using reporter and functional assays, we determined that expression of these miRNA-processing genes could be regulated by a subset of miRNAs and some miRNAs could target multiple miRNA biogenesis genes simultaneously. We also demonstrated that over-expression of these miRNAs inhibited cell proliferation and modulated the cell cycle in both Huh-7 human hepatoma cells and primary rat hepatocytes. From these observations, we postulated that selective up-regulation of miRNAs in the early-phase after PH was involved in the priming and commitment to liver regeneration, while the subsequent genome-wide down-regulation of miRNAs was required for efficient recovery of liver cell mass. Conclusion: Our data suggest that miRNA changes are regulated by negative feedback loops between miRNAs and their regulatory genes that may play an important role in the steady-state regulation of liver regeneration. Sham and Partial Hepatectomized livers at various time points.

ORGANISM(S): Homo sapiens

SUBMITTER: Yan Zeng

PROVIDER: E-GEOD-28404 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genomewide microRNA down-regulation as a negative feedback mechanism in the early phases of liver regeneration.

Shu Jingmin J Kren Betsy T BT Xia Zhilian Z Wong Phillip Y-P PY Li Lihua L Hanse Eric A EA Min Michael X MX Li Bingshan B Albrecht Jeffrey H JH Zeng Yan Y Subramanian Subbaya S Steer Clifford J CJ

Hepatology (Baltimore, Md.) 20110630 2

<h4>Unlabelled</h4>The liver is one of the few organs that have the capacity to regenerate in response to injury. We carried out genomewide microRNA (miRNA) microarray studies during liver regeneration in rats after 70% partial hepatectomy (PH) at early and mid time points to more thoroughly understand their role. At 3, 12, and 18 hours post-PH ∼40% of the miRNAs tested were up-regulated. Conversely, at 24 hours post-PH, ∼70% of miRNAs were down-regulated. Furthermore, we established that the ge ...[more]

PMID: 21574170

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Dataset Information

Genome-wide MicroRNA Downregulation as a Negative Feedback Mechanism in the Early Phases of Liver Regeneration

Publications

Genomewide microRNA down-regulation as a negative feedback mechanism in the early phases of liver regeneration.

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