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MiRNA expression changes in murine liver tumorigenesis

ABSTRACT: Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver’s unique affinity for small nucleic acids, miRNA based therapy has been proposed in the treatment of liver disease. There is thus an urgent need to identify and characterize aberrantly expressed miRNAs in HCC. In our study, we profiled miRNA expression changes in de novo liver tumors driven by MYC and/or RAS, two canonical oncogenes activated in a majority of human HCC.

ORGANISM(S): Oryza sativa Mus musculus Rattus norvegicus synthetic construct Homo sapiens Caenorhabditis elegans Populus trichocarpa

PROVIDER: GSE44570 | GEO | 2013/09/01

SECONDARY ACCESSION(S): PRJNA190086

REPOSITORIES: GEO

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miRNA expression changes in murine liver tumorigenesis

Project description:Hepatocellular carcinoma (HCC) is associated with poor survival for patients and few effective treatment options, raising the need for novel therapeutic strategies. MicroRNAs (miRNAs) play important roles in tumor development and show deregulated patterns of expression in HCC. Because of the liver’s unique affinity for small nucleic acids, miRNA based therapy has been proposed in the treatment of liver disease. There is thus an urgent need to identify and characterize aberrantly expressed miRNAs in HCC. In our study, we profiled miRNA expression changes in de novo liver tumors driven by MYC and/or RAS, two canonical oncogenes activated in a majority of human HCC. RNA from normal liver (LT2) and tumor tissue (LT2/MYC, LT2/RAS, LT2/MYC/RAS) was extracted, enriched for miRNAs and biotin-labeled using Ambion’s miRVana, flashPAGE and miRVana miRNA labeling kits respectively. Samples (n=4) from each genotype were hybridized to a custom Affymetrix Genechip designed to miRNA probes derived from Sanger miRBase v9.2. This array contained a total of 14216 probes, of which 672 matched to 301 unique mouse miRNAs. For each probe, an estimated background value was subtracted that was derived from the median signal of a set of GC-matched anti-genomic controls. Detection calls were based on a Wilcoxon rank-sum test of the miRNA probe signal compared to the distribution of signals from GC-content matched anti-genomic probes and normalized according to the variance stabilization method described.Post-normalized data scale is reported as generalized log2 data. For statistical hypothesis testing, one-way ANOVA was applied and probes are considered significantly differentially expressed based on a default p-value of 0.05 and log2 difference >1 or <-1.

2013-09-01 | E-GEOD-44570 | biostudies-arrayexpress

3-D culture cell lines mimic tumor in hepatocellular carcinoma

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2023-09-18 | PXD036831 | JPOST Repository

Aberrantly microRNA profiling in cancerous hepatocytes versus normal primary hepatocytes

Project description:MicroRNAs is a rapidly expanding area expected to change the way in which diseases will be diagnosed, treated and monitored in the future. Hepatocellular carcinoma (HCC) shows a rising incidence with high mortality but lack of effective targeted therapies. We identified the aberrantly expressed miRNAs involved in HCC through the comparison of miRNA expression profiling in cancerous hepatocytes with that in normal primary human hepatocytes and found 37 dysregulated miRNAs in HCC. These aberrantly expressed miRNAs may provide insights into pathogenesis of HCC and thus may be used for diagnosis and therapy. Over the past few years, though several studies have uncovered aberrant miRNA expression profiles in HCC compared with matched nonmalignant tissues, the overlap of deregulated miRNAs from different platforms is limited. To solve this problem, we recommend a method that using primary cancer cells or cancer cell lines and nonmalignant primary cells to identify the specific aberrantly miRNA expression profiles in HCC and even in other types of cancer. Here, we identified the aberrantly expressed miRNAs involved in hepatoma through the comparison of miRNA expression profiling in cancerous hepatocytes with that in normal primary human hepatocytes and 37 dysregulated miRNAs were screened out by 2-fold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs whose fold changes were over 15-fold change exhibited significantly differential expression pattern between the cancerous and normal hepatocytes.

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Successful and failed human liver regeneration are characterized by the coordinated expression of distinct microRNAs

Project description:The liver’s remarkable capacity to regenerate allows it to carry out vital life-supporting functions despite unrelenting pathogen and toxin-induced injury. Unchecked, this capability also leads to cirrhosis, a burgeoning global disease burden. Existing animal models only partially recapitulate human liver regeneration, which hitherto has not been systematically studied. We investigated human liver regeneration in a unique model of liver transplantation. Here we show coordinated changes in expression of microRNA (miRNA) during regeneration that drive proliferation, innate immunity and angiogenesis. Failed regeneration is associated with distinct miRNAs enforcing cell cycle inhibition and DNA methylation. The miRNA expression associated with successful or failed regeneration when recapitulated in vitro, triggered expression of cardinal regeneration-linked genes promoting cell cycle entry or inhibition, respectively. Furthermore, inhibition of three miRNAs whose downregulation is associated with successful regeneration, induced proliferation in vitro. Our data indicate that human liver regeneration is orchestrated by distinct miRNAs determining cell cycle fate. Their manipulation may obviate the need for transplantation by enforcing successful regeneration in the liver and other solid organs.

2013-05-06 | GSE36146 | GEO

Transcriptome profile of liver biopsy tissues from patients with non-alcoholic fatty liver disease (tissue validation set 2).

Project description:Non-alcoholic fatty liver disease (NAFLD) is a major global health problem with its high prevalence and risk of developing lethal complications, progressive liver fibrosis and hepatocellular carcinoma (HCC), the only rising cancer mortality in the U.S. For early HCC detection to improve the dismal prognosis, there is an urgent unmet need to identify a subset of NAFLD patients with elevated risk of HCC. Herein, we derived a hepatic-transcriptome-based NAFLD-specific HCC risk biomarker, PLS-NAFLD, and validated it in two independent cohorts of HCC-naive and experienced NAFLD patients..

2022-07-01 | GSE193080 | GEO

Transcriptome profile of liver biopsy tissues from patients with non-alcoholic fatty liver disease (derivation set).

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Transcriptome profile of liver biopsy tissues from patients with non-alcoholic fatty liver disease (tissue validation set 1).

2022-07-01 | GSE193066 | GEO

Aberrantly microRNA profiling in cancerous hepatocytes versus normal primary hepatocytes

2010-12-30 | GSE20077 | GEO

Identifying novel drivers of human hepatocellular carcinoma and revealing clinical relevance as early diagnostic and prognostic biomarker

Project description:Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and is the one of the few cancers in which a continued increase in incidence has been observed over several years. HCC associated with chronic liver disease evolves from precancerous lesion and early HCC to overt cancer, and identifying key molecules contributing to early stage HCC is an urgent need. We aim to determine transcriptome-based molecular signature of multistep hepatocarcinogenesis, and to identify novel biomarkers to diagnose and predict early stage HCC.

2017-12-31 | GSE89377 | GEO

Differential miRNA expression profiles betweenHBV-related HCC tumor versus non-tumor liver tissue

Project description:miRNA played an important role in the process of carcinogenesis in HBV related hepatocellular carcinoma. Therefore, we performed miRNA microarray to evaluate the miRNAs that expressed differentially between HCC tumor versus non-tumor liver tissues. RNA was extracted from snap fresh tissue collected from resected HCC tumor and adjacent non-tumor liver tissues. All HCC tumors were HBV-associated HCC.

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