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Series GSE102417 Query DataSets for GSE102417
Status Public on Sep 19, 2018
Title A comparative miRNA/mRNA analysis in distinct murine liver cancer models reveals miR-193a-5p and NUSAP1 as therapeutic targets in HCC [miRNA]
Platform organisms Mus musculus; Rattus norvegicus
Sample organism Mus musculus
Experiment type Expression profiling by RT-PCR
Summary BACKGROUND & AIMS: We performed an integrated analysis to identify microRNAs (miRNAs) and mRNAs with altered expression in liver tumors from 3 mouse models of hepatocellular carcinoma (HCC) and human tumor tissues.
METHODS: We analyzed miRNA and mRNA expression profiles of liver tissues from mice with diethylnitrosamine-induced hepatocarcinogenesis, conditional expression of lymphotoxin alpha and lymphotoxin beta , or inducible expression of a Myc transgene (Tet-O-Myc mice), as well as male C57BL/6 mice (controls). miRNA mimics were expressed and miRNAs and mRNAs were knocked down in human (Huh7, Hep3B, JHH2) hepatoma cell lines; cells were analyzed for viability, proliferation, apoptosis, migration, and invasion. Cells were grown as xenograft tumors in nude mice and analyzed. We combined in-silico target gene prediction with mRNA profiles from all 3 mouse models. We quantified miRNA levels in 146 fresh-frozen tissues from patients (125 HCCs, 17 matched non-tumor tissues, and 4 liver samples from patients without cancer) and published human data sets and tested correlations with patient survival times using Kaplan-Meier curves and the log-rank test. Levels of NUSAP1 mRNA were quantified in 237 HCCs and 5 non-tumor liver samples using the Taqman assay.
RESULTS: Levels of the microRNA 193a-5p (MIR193A-5p) were reduced in liver tumors from all 3 mouse tumor models and in human HCC samples, compared with non-tumor liver tissues. Expression of a MIR193A-5p mimic in hepatoma cells reduced proliferation, survival, migration, and invasion and their growth as xenograft tumors in nude mice. We found nucleolar and spindle associated protein 1 (NUSAP1) to be a target of MIR193A-5p; HCC cells and tissues with low levels of MIR193A-5p had increased expression of NUSAP1. Increased levels of NUSAP1 in HCC samples correlated with shorter survival times of patients. Knockdown of NUSAP1 in Huh7 cells reduced proliferation, survival, migration, and growth as xenograft tumors in nude mice. Hydrodynamic tail-vein injections of a small hairpin RNA against NUSAP1 reduced growth of AKT1-MYC-induced tumors in mice.
CONCLUSIONS: MIR193A-5p appears to prevent liver tumorigenesis by reducing levels of NUSAP1. Levels of MIR193A-5p are reduced in mouse and human HCC cells and tissues, leading to increased levels of NUSAP1, associated with shorter survival times of patients. Integrated analyses of miRNAs and mRNAs in tumors from mouse models can lead to identification of therapeutic targets in humans.
 
Overall design qPCR miRNA expression profiling. miRNA expression was profiled in three pathogenically distinct murine hepatocellular carcinoma models
 
Contributor(s) Roy S, Hooiveld GJ, Roderburg C, Luedde T
Citation(s) 30165047
Submission date Aug 09, 2017
Last update date Jul 25, 2021
Contact name Guido Hooiveld
E-mail(s) guido.hooiveld@wur.nl
Organization name Wageningen University
Department Div. Human Nutrition & Health
Lab Nutrition, Metabolism & Genomics Group
Street address HELIX, Stippeneng 4
City Wageningen
ZIP/Postal code NL-6708WE
Country Netherlands
 
Platforms (1)
GPL22525 Applied Biosystems TaqMan OpenArray Rodent MicroRNA Panel
Samples (34)
GSM2736274 miRNA_DEN, control, replicate 1
GSM2736275 miRNA_DEN, control, replicate 2
GSM2736276 miRNA_DEN, control, replicate 3
This SubSeries is part of SuperSeries:
GSE102418 A comparative miRNA/mRNA analysis in distinct murine liver cancer models reveals miR-193a-5p and NUSAP1 as therapeutic targets in HCC
Relations
BioProject PRJNA397722

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE102417_Feature_category.txt.gz 10.6 Kb (ftp)(http) TXT
GSE102417_Non-normalized_data.txt.gz 34.9 Kb (ftp)(http) TXT
GSE102417_RAW.tar 1.2 Mb (http)(custom) TAR (of TXT)
GSE102417_normalized_data.txt.gz 17.0 Kb (ftp)(http) TXT
Raw data provided as supplementary file
Processed data are available on Series record
Raw data are available on Series record

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