Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio)

Her, Guor Mour; Hsu, Chia-Chen; Hong, Jiann Ruey; Lai, Chien-Yu; Hsu, Meng Chieh; Pang, Hsi Wen; Sheng, Chan; Pai, Wan Yu

doi:10.1016/j.bbalip.2011.06.011

Cited by 63 publications

(48 citation statements)

References 71 publications

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“…Pathway analysis of these genes confirmed the previous observations that Gankyrin regulates p53, C/EBPa, and HIFa-dependent gene expression. Recent study using transgenic zebrafish revealed that Gankyrin overexpression induced liver steatosis and modulated gene and microRNA expression (46). Together, these studies suggest an important role of Gankyrin in regulating gene transcription.…”

Section: Discussionmentioning

confidence: 89%

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Bai

Tai

et al. 2013

Cancer Research

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Hepatic metastasis is responsible for the majority of colorectal cancer (CRC)-related mortalities. Although Gankyrin (PSMD10) has been implicated in cancer metastasis, its exact role and underlying mechanisms of CRC hepatic metastasis remain largely unknown. Herein, we showed that the expression of Gankyrin was higher in primary CRC with hepatic metastasis compared with CRC without metastasis. RNAi-mediated silencing of Gankyrin expression in highly metastatic human CRC cells impaired their migratory and metastatic capacity in vivo. Genome-wide transcriptome profiling revealed activation of the interleukin (IL)-8 signaling pathway by Gankyrin. Protein levels of IL-8 and cyclin D1 (CCND1), the two important molecules in the IL-8 pathway, were positively correlated with Gankyrin expression in human CRC specimens. Furthermore, genetic deletion of cyclin D1 showed its requirement in Gankyrin-mediated cell migration. Finally, administration of recombinant IL-8 rescued the migratory defect of CRC cells where Gankyrin expression was silenced. Together, our findings highlight the importance of Gankyrin in hepatic metastasis of CRC and point out its candidature as a potential prognostic marker and therapeutic target to improve the clinical management of metastatic CRC. Cancer Res; 73(14); 4548-58. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 89%

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Bai

Tai

et al. 2013

Cancer Research

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“…This finding is not surprising, as miRNAs have been shown to postranscriptionally regulate metabolic target genes directly or indirectly through important signaling pathways involved in the coordination of cellular metabolism (Tibiche and Wang, 2008). Indeed, preliminary evidence suggests that their roles in fish metabolism may be conserved (Her et al, 2011;Mennigen et al, 2012), in line with the highly conserved nature of many miRNAs in the vertebrate lineage (Lee et al, 2007). With this increasing availability of molecular tools, we wanted to determine for the first time the underlying molecular mechanisms (mRNAs and miRNAs) that are associated with the transition between endogenous (vitellus) and exogenous (diet) feeding in rainbow trout alevins.…”

Section: Introductionmentioning

confidence: 85%

“…For example, miRNA-29, miRNA-103 and miRNA-107 have been shown to inhibit insulin-induced Akt signaling, in effect stimulating gluconeogenic gene expression in the liver with consequences for glucose homeostasis in mammalian models (Pandey et al, 2011;Trajkovski et al, 2011;Jordan et al, 2011). While direct mechanistic evidence for similar roles in fish is still lacking, correlational descriptive studies reveal a possible conservation of these functions in fish (Her et al, 2011;Mennigen et al, 2012). In our study, no changes were observed in the expression of miR-103/107 in trout using different feeding strategies in spite of an evident regulation of some gluconeogenic genes.…”

Section: Ontogenic Changes In Ubiquitously Expressed Mirnas With Metamentioning

confidence: 99%

Ontogenesis of expression of metabolic genes and microRNAs in rainbow trout alevins during the transition from the endogenous to the exogenous feeding period

Mennigen

Skiba‐Cassy

Panserat

2013

Journal of Experimental Biology

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SUMMARYAs oviparous fish, rainbow trout change their nutritional strategy during ontogenesis. This change is divided into the exclusive utilization of yolk-sac reserves (endogenous feeding), the concurrent utilization of yolk reserves and exogenous feeds (mixed feeding) and the complete dependence on external feeds (exogenous feeding). The change in food source is accompanied by well-characterized morphological changes, including the development of adipose tissue as an energy storage site, and continuous muscle development to improve foraging. The aim of this study was to investigate underlying molecular mechanisms that contribute to these ontogenetic changes between the nutritional phenotypes in rainbow trout alevins. We therefore analyzed the expression of marker genes of metabolic pathways and microRNAs (miRNAs) important in the differentiation and/or maintenance of metabolic tissues. In exogenously feeding alevins, the last enzyme involved in glucose production (g6pca and g6pcb) and lipolytic gene expression (cpt1a and cpt1b) decreased, while that of gk, involved in hepatic glucose use, was induced. This pattern is consistent with a progressive switch from the utilization of stored (gluconeogenic) amino acids and lipids in endogenously feeding alevins to a utilization of exogenous feeds via the glycolytic pathway. A shift towards the utilization of external feeds is further evidenced by the increased expression of omy-miRNA-143, a homologue of the mammalian marker of adipogenesis. The expression of its predicted target gene abhd5, a factor in triglyceride hydrolysis, decreased concurrently, suggesting a potential mechanism in the onset of lipid deposition. Muscle-specific omy-miRNA-1/133 and myod1 expression decreased in exogenously feeding alevins, a molecular signature consistent with muscle hypertrophy, which may be linked to nutritional cues or increased foraging.Supplementary material available online at http://jeb.biologists.org/cgi/content/full/216/9/1597/DC1 Key words: metabolism, microRNA, nutrition. THE JOURNAL OF EXPERIMENTAL BIOLOGY 1598or the potential role of miRNA in the acquisition of the capacity to utilize external feeds. Specifically, we assessed potential changes in global intermediary metabolism between nutritional phenotypes by investigating the expression of genes of glucose metabolism (glycolysis and gluconeogenesis), lipid metabolism (lipogenesis and β-oxidation) and amino acid metabolism (amino acid catabolism). Additionally, we investigated the expression of specific miRNAs and their predicted target genes, whose function in metabolic tissues has been characterized in mammalian models (Rottiers and Näär, 2012). The miRNAs investigated in this study have either been associated with the differentiation and function of specific metabolic tissues in mammals, such as a role for miR-33 and miR-122 in proliferation and lipid metabolism in the liver (Cirera-Salinas et al., 2012;Elmén et al., 2008), a role for miRNA-143 in the differentiation of adipose tissue (Esau et al., 2004) and miR-1...

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“…In this model, transgenic over-expression of gankyrin, a small ankyrin-repeat protein that plays a role in cellular proliferation, led to increased lipid content in > 90% of viable adult fish. Overexpression of gankyrin led to the development of hepatic steatosis and was associated with increased levels of miR-16, miR-122, and miR-126, and decreased miR-27b [29] . This study provides evidence supporting a link between gankyrin and miRNAs in modulating the development of hepatic steatosis in zebrafish; however, the role of this network in humans is not yet known.…”

Section: In Vivo Studiesmentioning

confidence: 99%

Micro RNAs in the development of non-alcoholic fatty liver disease

Gerhard

DiStefano

2014

WJH

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Nonalcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD) refers to a group of disorders that arise from the accrual of fat in hepatocytes. Although various factors have been associated with the development of NAFLD, including genetic predisposition and environmental exposures, little is known about the underlying pathogenesis of the disease. Research efforts are ongoing to identify biological targets and signaling pathways that mediate NAFLD. Emerging evidence has implicated a role for micro RNAs (miRNAs), short single-stranded molecules that regulate gene expression either transcriptionally, through targeting of promoter regions, or post-transcriptionally, by blocking translation or promoting cleavage of specific target mRNAs. Several miRNAs have been associated with NAFLD, although our understanding of the biology underlying their role is still emerging. The goal of this review is to present an overview of the current state of knowledge of miRNAs involved in the development of NAFLD across a range of in vitro and in vivo models, including miRNAs that contribute to pathological mechanisms related to fatty liver in humans. Much less is known about the specific targets of miRNAs in cells, nor the molecular mechanisms involved in the development and progression NAFLD and related outcomes. More recently, the identification and validation of miRNA signatures in serum may facilitate the development of improved methods for diagnosis and clinical monitoring of disease progression. Core tip: Available data on miRNAs in nonalcoholic fatty liver disease (NAFLD) are largely derived from various cell culture and animal models. Reflecting an emerging field, little cross-model concordance is present and few human data are available for comparison with cell culture and animal model results. Although the generation of human data may be limited by the availability of tissue samples, recent reports of circulating miRNAs from NAFLD patients hold promise for significant progress for diagnosis and clinical MINIREVIEWSSubmit a

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Overexpression of gankyrin induces liver steatosis in zebrafish (Danio rerio)

Cited by 63 publications

References 71 publications

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Ontogenesis of expression of metabolic genes and microRNAs in rainbow trout alevins during the transition from the endogenous to the exogenous feeding period

Micro RNAs in the development of non-alcoholic fatty liver disease

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