Surgical Department, Medical School, University of Patras, 26504 Patras, Greece.
Int J Mol Med. 2012 May;29(5):747-55. doi: 10.3892/ijmm.2012.902. Epub 2012 Feb 3.
Liver is uniquely capable to repair itself after injury. Multiple molecular and biochemical processes initiated after partial hepatectomy, lead to proliferation of all cells within the liver. MicroRNAs (miRNAs) are a class of highly abundant non-coding RNA molecules that cause post-transcriptional gene repression and are involved in several biological processes including cell cycle regulation and differentiation. In this study, we examined the expression levels of miRNAs in liver tissue received from control mice (L0) and compared them with the corresponding levels in liver tissue 12 h after liver regeneration induced by 2/3 partial hepatectomy (L12). MiRNA expression was investigated using microRNA profiling. Further qPCR analysis was used for validation of the differentially expressed miRNAs at an early stage of liver regeneration, induced by 2/3 partial hepatectomy. TargetScan and Gene Ontology (GO) analyses were performed in order to identify the possible miRNA target genes and their ontology, respectively. A subset of miRNAs was found to be differentially expressed during liver regeneration. Mmu-miR-21 and mmu-miR-30b* showed the higher levels of up-regulation in liver tissue from the hepatectomized mice at the end of the experiment (L12) compared to the sham operated mice (L0). Mmu-miR-21 up-regulation was further confirmed by qPCR. In situ hybridization (ISH) revealed that mmu-miR-21 exhibited the higher levels of expression at 12 h post hepatectomy. On the contrary, mmu-miR-34c*, mmu-miR-144, mmu-miR-207, mmu-miR-207, mmu-miR-451, mmu-miR-582-3p and mmu-miR-290-5p exhibited <0.5 down-regulation in liver tissue after partial hepatectomy in L12 vs. L0 mice. The results from microarray and qPCR analyses were in good agreement. In conclusion, our results provide important information regarding the differentially expressed miRNAs in murine liver tissue before and after partial hepatectomy. The early up-regulation of mmu-miR-21 during the process of liver regeneration suggests a regulatory role in liver regeneration in vivo.
肝脏具有独特的自我修复能力。肝部分切除术后，多种分子和生化过程启动，导致肝脏内所有细胞增殖。微小 RNA（miRNA）是一类高度丰富的非编码 RNA 分子，可引起转录后基因沉默，并参与包括细胞周期调控和分化在内的多种生物学过程。在这项研究中，我们检查了来自对照小鼠（L0）的肝组织中的 miRNA 表达水平，并将其与肝再生诱导的肝部分切除术后 12 小时（L12）肝组织中的相应水平进行了比较。使用 microRNA 谱分析研究了 miRNA 的表达。进一步的 qPCR 分析用于验证肝再生早期（肝部分切除术后 2/3）诱导的差异表达 miRNA。为了分别鉴定可能的 miRNA 靶基因及其本体，进行了 TargetScan 和基因本体论（GO）分析。在肝再生过程中发现一组 miRNA 表达存在差异。在实验结束时（L12），与 sham 手术小鼠（L0）相比，肝部分切除术后小鼠肝组织中 Mmu-miR-21 和 Mmu-miR-30b* 的上调水平更高。qPCR 进一步证实了 Mmu-miR-21 的上调。原位杂交（ISH）显示，Mmu-miR-21 在肝切除后 12 小时表达水平更高。相反，Mmu-miR-34c*、Mmu-miR-144、Mmu-miR-207、Mmu-miR-451、Mmu-miR-582-3p 和 Mmu-miR-290-5p 在肝部分切除术后 L12 与 L0 小鼠的肝组织中下调<0.5。微阵列和 qPCR 分析的结果非常吻合。总之，我们的研究结果为肝部分切除术前和术后小鼠肝组织中差异表达的 miRNA 提供了重要信息。Mmu-miR-21 在肝再生过程中的早期上调表明其在体内肝再生中具有调节作用。
