Ontology highlight
ABSTRACT:
PROVIDER: PRJNA554498 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9678930_1.fastq.gz | Fastqsanger.gz | |||
| SRR9678930_2.fastq.gz | Fastqsanger.gz |
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Project description:Notch intracellular domain (NICD) is the active form of the Notch receptor. In this mouse model, NICD is inserted in the Rosa26 locus downstream of a loxP-STOP-LoxP (lsl) sequence and therefore NICD expression is dependant on Cre recombinase expression (Mono transgenic control Rosa26-lsl-NICD) . These mice are crossed with the AFP-Cre strain that expresses Cre in hepatoblasts due to its regulation by the AFP promoter and albumin enhancer (Double transgenic mutant AFP-Cre/Rosa26-lsl-NICD). Newborn mice at day 0 and day 2 are sacrificed and liver RNA samples from control monotransgenic Rosa26-lsl-NICD and from bitransgenic AFP-Cre/Rosa26-lsl-NICD (AFP-NICD) are obtained. Whole genome expression profiling of these samples is submitted.
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Project description:Increased α-fetoprotein (AFP) levels have been reported to predict a poor prognosis in hepatocellular carcinoma (HCC). We assessed the mechanism of AFP involvement in the progression of HCC and determined whether AFP could be a molecular target. We used human HCC cell lines to assess proliferation and apoptosis response to exogenous AFP. We introduced AFP small interfering RNA (siRNA) into HCC cell lines to examine whether it could inhibit cell proliferation and anti-apoptotic properties. The effects of systemically introduced AFP siRNA were assessed using a tumor xenotransplantation model. The effects of AFP on gene expression in HCC cell lines and human HCC specimens were examined. Exogenous AFP induced cell proliferation dose-dependently and inhibited apoptosis induced by 5-fluorouracil (5-FU) in all cell lines examined. AFP siRNA inhibited the proliferation of AFP-producing HCC cell lines and induced apoptosis in co-cultures with 5-FU. Tumor sizes in mice treated with AFP siRNA were significantly smaller than those in controls. AFP siRNA administration in mice induced a low proliferation index and a high apoptosis index in tumors. cDNA microarray analysis, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot using HepG2 and HLE cells with AFP showed that AFP reduced expression of genes related to apoptosis (DFFB) and tumor suppression (NDRG2). Expression of these molecules was also suppressed in human HCC tissues that overexpress AFP. AFP is not only a passive tumor marker, but also an active tumor stimulator through several mechanisms. AFP siRNA introduction may be of possible therapeutic use for HCC. Keywords: Genetic modification
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Project description:Notch intracellular domain (NICD) is the active form of the Notch receptor. In this mouse model, NICD is inserted in the Rosa26 locus downstream of a loxP-STOP-LoxP (lsl) sequence and therefore NICD expression is dependant on Cre recombinase expression (Mono transgenic control Rosa26-lsl-NICD) . These mice are crossed with the AFP-Cre strain that expresses Cre in hepatoblasts due to its regulation by the AFP promoter and albumin enhancer (Double transgenic mutant AFP-Cre/Rosa26-lsl-NICD). Newborn mice at day 0 and day 2 are sacrificed and liver RNA samples from control monotransgenic Rosa26-lsl-NICD and from bitransgenic AFP-Cre/Rosa26-lsl-NICD (AFP-NICD) are obtained. Whole genome expression profiling of these samples is submitted. Five liver samples from Control mice and six liver samples from Mutant mice are analyzed using the Agilent Whole Mouse Genome Oligo Microarray G4122A platform. Array data was preprocessed and analyzed using GenePattern software and R.
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