Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy

Raschzok, Nathanael; Werner, Wiebke; Sallmon, Hannes; Billecke, Nils; Dame, Christof; Neuhaus, P.; Sauer, Igor M.

doi:10.1152/ajpregu.00632.2010

Cited by 33 publications

(38 citation statements)

References 30 publications

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“…Our finding of mmu-miR-207 repression is in agreement with a recent study that showed that miR-207 is down-regulated during rat liver regeneration (29).…”

Section: Discussionsupporting

confidence: 93%

MicroRNA profiling in murine liver after partial hepatectomy

Habeos

2012

Int J Mol Med

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Abstract. 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 downregulation 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. IntroductionPartial hepatectomy (PH) represents the most commonly used model for the study of liver regeneration. It is a very complex and well-orchestrated phenomenon that is carried out by the participation of all mature liver cell types. The extent of hepatocyte proliferation is directly proportional to the amount of resected liver tissue and 2/3 partial hepatectomy (2/3 PH) leads to a highly synchronized hepatocyte cell-cycle entry and progression. The first phase, known as the 'priming phase', occurs in the first hours after PH and poises the hepatocytes to enter the G1 phase and to become receptive to growth factors. The second phase corresponds to an increased metabolic demand imposed on the remnant liver. During this phase, among other metabolic changes, transient hypoglycemia is suggested to induce systemic lipolysis followed by a lipid droplets accumulation in the hepatocytes. Between 36-42 h after 2/3 PH, most hepatocytes are in the S phase of the cell cycle. The rem...

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“…Our finding of mmu-miR-207 repression is in agreement with a recent study that showed that miR-207 is down-regulated during rat liver regeneration (29).…”

Section: Discussionsupporting

confidence: 93%

MicroRNA profiling in murine liver after partial hepatectomy

Habeos

2012

Int J Mol Med

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“…microRNAs have been shown to function as negative regulators of many genes during ovary development (Carletti et al 2010, Xu et al 2011b. The regulation of Pcna expression by microRNAs has been mentioned in several studies (Han et al 2010, Sirotkin et al 2010, Raschzok et al 2011. For example, downregulation of Dicer1 was associated with enhanced expression of Pcna in human cancer cell lines (Han et al 2010), and a total of 53 microRNAs were shown to most likely repress the expression of Pcna in cultured human granulosa cells (Sirotkin et al 2010).…”

Section: Discussionmentioning

confidence: 99%

microRNA 376a regulates follicle assembly by targeting Pcna in fetal and neonatal mouse ovaries

Zhang¹,

Jiang²,

Zhang³

et al. 2014

Reproduction

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In mammals, the primordial follicle pool, providing all oocytes available to a female throughout her reproductive life, is established perinatally. Dysregulation of primordial follicle assembly results in female reproductive diseases, such as premature ovarian insufficiency and infertility. Female mice lacking Dicer1 (Dicer), a gene required for biogenesis of microRNAs, show abnormal morphology of follicles and infertility. However, the contribution of individual microRNAs to primordial follicle assembly remains largely unknown. Here, we report that microRNA 376a (miR-376a) regulates primordial follicle assembly by modulating the expression of proliferating cell nuclear antigen (Pcna), a gene we previously reported to regulate primordial follicle assembly by regulating oocyte apoptosis in mouse ovaries. miR-376a was shown to be negatively correlated with Pcna mRNA expression in fetal and neonatal mouse ovaries and to directly bind to Pcna mRNA 3 0 untranslated region. Cultured 18.5 days postcoitum mouse ovaries transfected with miR-376a exhibited decreased Pcna expression both in protein and mRNA levels. Moreover, miR-376a overexpression significantly increased primordial follicles and reduced apoptosis of oocytes, which was very similar to those in ovaries co-transfected with miR-376a and siRNAs targeting Pcna. Taken together, our results demonstrate that miR-376a regulates primordial follicle assembly by modulating the expression of Pcna. To our knowledge, this is the first microRNA-target mRNA pair that has been reported to regulate mammalian primordial follicle assembly and further our understanding of the regulation of primordial follicle assembly.

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“…Other studies have addressed the role of miRNAs during hepatic carcinogenesis [43] and during hepatic regeneration following partial hepatectomy. Several studies, including our own, have shown that liver regeneration is associated with specific profiles of miRNA expression changes, which can be correlated with expression changes in target genes that play important roles in liver regeneration, such as growth factors or cell-cycle regulators [44][45][46][47][48][49].…”

Section: Micrornas In the Livermentioning

confidence: 88%