Parkin as a Tumor Suppressor Gene for Hepatocellular Carcinoma
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE9651 | GEO | 2007/11/30
SECONDARY ACCESSION(S): PRJNA103519
REPOSITORIES: GEO
Similar Datasets
Project description:To provide an insight into the molecular mechanism by which parkin deficiency contributes to hepatocarcinogenesis, we analyzed gene expression profiles of nontumorous and tumorous liver tissues from parkinâ/â mice using cDNA microarray analyses. Experiment Overall Design: We analysed the up and down regulated genes in tumorous and non-tumorous liver tissues of parkin-/- mice compared with normal liver tissues of wild-type mice.
2008-06-16 | E-GEOD-9651 | biostudies-arrayexpress
Project description:Purpose: The E3 ubiquitin ligase Parkin is a well-characterized regulator of mitochondrial autophagy (mitophagy); however, it is becoming increasingly appreciated to perform additional roles in various compartments of the cell. Our laboratory confirmed the presence of Parkin in the nucleus of various tissues (biochemical fractionations) and cell types (immunofluorescent imaging). Hypoxia-induced nuclear translocation of Parkin occured independent of the mitophagy regulator PINK1, and Parkinson's disease-associated mutants were restricted from the nuclueus. Accordingly, we inserted a nuclear localization sequence (NLS) at the n-terminus of Parkin and overexpressed both NLS Parkin and the wild-type protein in HeLa cells cultured at normoxia and hypoxia. Next-generation RNA-sequencing (RNA-seq) was used to determine the effect of nuclear Parkin on cellular transcription. Methods: mCherry-tagged NLS and wild-type Parkin were overexpressed in HeLa cells. Differential expression analyses were performed on Parkin vs. mCherry control cells and NLS Parkin vs. mCherry control cells at normoxia and following 12hr of hypoxia (n=3/group/condition). Paired-end sequencing was performed using the HiSeq4000. FastQC v0.11.3 was used for quality control, Trimmomatic v0.36 was used to trim reads which were aligned to the human genome (GRCh37.p13) using the STAR aligner v2.5.3a. Read quantification was performed with RSEM v 1.3.0 and the Gencode release 19. The R BioConductor packages edgeR and limma were used to implement the limma-voom method for differential expression analysis. Results: During normoxia, Parkin had no effect on basal transcription; however, overexpression of NLS Parkin was associated with 168 differentially expressed genes (DEGs: fold-change </= 1.5, FDR < 0.05) relative to mCherry control cells. Following hypoxia, the transcriptome associated with the overexpression of wild-type Parkin more closely resembled that of NLS Parkin. Along these lines, Parkin overexpression during hypoxia coincided with a total of 158 DEGs, 37% of which were shared with NLS Parkin. Overlapping and shared DEGs among Parkin and NLS Parkin were implicated in cellular metabolism, HIF1 signaling and survival. Our follow up co-immunoprecipitation and real-time quantitative PCR studies demonstrated that Parkin interacts with the Estrogen Related Receptor Alpha (ERRa) to promote the induction of its downstream target genes. Conclusions: Nuclear translocation of Parkin is a novel means by which this cytoprotective protein contributes to cellular homeostasis and especially critical during hypoxia.
2019-11-06 | GSE139989 | GEO
Project description:Six pairs of hepatocellular carcinoma and their corresponding non-tumrous liver parenchymas were analyzed to identify the genes differentially expressed in hepatocellular carcinoma and nontumorous liver parenchyma.
2013-04-27 | GSE46408 | GEO
Project description:Expression profiling of tumor and adjacent non-tumorous tissues of Hepatocellular Carcinoma (HCC) patients. Illumina HumanHT-12 V4.0 expression beadchip was used to obtain expression profiles across more than 31,000 annotated genes. Samples included 59 tumors and 59 adjacent non-tumorous samples. Total RNA obtained from the 39 tumors and 39 adjacent non-tumorous samples
2014-12-10 | E-GEOD-57957 | biostudies-arrayexpress
Project description:Expression profiling of tumor and adjacent non-tumorous tissues of Hepatocellular Carcinoma (HCC) patients. Illumina HumanHT-12 V4.0 expression beadchip was used to obtain expression profiles across more than 31,000 annotated genes. Samples included 59 tumors and 59 adjacent non-tumorous samples.
2014-12-10 | GSE57957 | GEO
Project description:DNA methylation profiling of tumor and adjacent non-tumorous tissues of Hepatocellular Carcinoma (HCC) patients. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 59 tumors and 59 adjacent non-tumorous samples.
2014-12-10 | GSE57956 | GEO
Project description:DNA methylation profiling of tumor and adjacent non-tumorous tissues of Hepatocellular Carcinoma (HCC) patients. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 59 tumors and 59 adjacent non-tumorous samples. Bisulphite converted DNA from the 59 tumors and 59 adjacent non-tumorous samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip.
2014-12-10 | E-GEOD-57956 | biostudies-arrayexpress
Project description:Mutations in the parkin gene, which encodes a ubiquitin ligase, are a major genetic cause of parkinsonism. Interestingly, parkin also plays a role in cancer as a putative tumor suppressor, and the gene is frequently targeted by deletion and inactivation in human malignant tumors. Here, we investigated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells. Restoration of parkin expression promoted G1 phase cell cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Notably, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin null mouse model exhibited increased levels of cyclin D1, VEGF receptor and Akt phosphorylation and divided significantly faster when compared with wild type cells, with suppressionof these changes following parkin re-introduction. Clinically, analysis of parkin pathway activation was predictive for the survival outcome of glioma patients. Taken together, our study provides mechanistic insight into the tumor suppressor function of parkin in brain tumors, and suggests that measurement of parkin pathway activation may be used clinically as a prognostic tool in brain tumor patients.
2012-03-15 | GSE29494 | GEO
Project description:Dysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and a potential genetic mechanism of cardiomyopathy. Despite epidemiological associations between Parkinson disease and heart failure, the role of Parkin and mitophagic quality control in maintaining normal cardiac homeostasis is poorly understood.We used germline mutants and cardiac-specific RNA interference to interrogate Parkin regulation of cardiomyocyte mitochondria and examine functional crosstalk between mitophagy and mitochondrial dynamics in Drosophila heart tubes.
2015-10-31 | GSE74517 | GEO
Project description:Dysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and a potential genetic mechanism of cardiomyopathy. Despite epidemiological associations between Parkinson disease and heart failure, the role of Parkin and mitophagic quality control in maintaining normal cardiac homeostasis is poorly understood.We used germline mutants and cardiac-specific RNA interference to interrogate Parkin regulation of cardiomyocyte mitochondria and examine functional crosstalk between mitophagy and mitochondrial dynamics in Drosophila heart tubes. 5 wild-type mouse hearts; 4 germline Parkin knockout mouse hearts Please note that the mouse cardiac examples were an adjunct to the Drosophila studies that comprised most of the associated publication. However, mRNA-sequencing was only performed on the mouse samples, not the Drosophila heart tubes.
2015-10-31 | E-GEOD-74517 | biostudies-arrayexpress