Z Gastroenterol 2013; 51 - P_3_18
DOI: 10.1055/s-0032-1332013

Microrna MIR-352 in early liver regeneration: What role?

SL Lisboa 1, N Raschzok 1, A Leder 1, N Schlüter 1, M Jörres 1, S Kolano 1, A Butter 1, S Lippert 1, W Werner 1, P Neuhaus 1, IM Sauer 1
  • 1Charité – Universitätsmedizin Berlin, General, Visceral, and Transplant Surgery, Experimental Surgery and Regenerative Medicine, Berlin, Germany

Objectives:

The liver possesses the unique capability to regenerate. Evidence shows that certain miRNAs are differently expressed during liver regeneration. In a previous microarray study, miR-352 was found to be early downregulated following rat partial hepatectomy. The aim of this study is to identify the role played by miR-352 and its putative targets in the early phase of liver regeneration.

Materials & Methods:

Putative targets of miR-352 were predicted in silico using TargetScan and miRanda. In vitro inhibition and mimicry of miR-352 was performed in primary rat hepatocytes. Proteomic analysis was carried out using 2DE gels and significantly regulated spots were identified using mass spectrometry. In silico and in vitro results were compared and relevant matches were further analyzed through real-time PCR and western blot.

Results: In silico target prediction of miR-352 revealed a total of 1104 (TargetScan) and 749 (miRanda) putative targets. In addition, 2DE gels revealed 9 significantly regulated spots and proteomic analysis revealed 205 relevant protein hits. Among the matched targets were carbonic anhydrase (CA3) and hydroxymethylglutaryl-CoA synthase (HMGCS2), both highly expressed in the liver. Although western blot analysis did not show significant regulation of the mentioned targets, RT-PCR results showed a significant regulation of CA3.

Conclusions:

Transfection with miR-352 anti-mirs and mimics regulated the protein expression pattern in primary rat hepatocytes. miR-352 seems to play an important role in early liver regeneration by targeting CA3, a known player in the liver response to oxidative stress. We believe that future therapies targeting microRNA regulation in patients undergoing partial liver hepatectomy might have a direct impact on the outcome of the liver regeneration process. Further in vitro and in vivo studies will be necessary to further investigate the putative role of miR-352 in oxidative stress response and liver regeneration.