Transcriptomic analysis of ATG5 induced hepatocellular carcinoma in zebrafish
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE278167 | GEO | 2026/06/01
REPOSITORIES: GEO
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Project description:Autophagy plays an important role in physiology and tumorigenesis. We and others have demonstrated that Ha-ras overexpression induces autophagy in NIH3T3 cells. Autophagic machinery is regulated by a family of autophagy associated genes (Atg). The inducible Ha-ras oncogene was introduced into mouse embryo fibroblast Atg5 wild type [MEF-Atg5(+/+)] and Atg5 knock-out [MEF-Atg5(-/-)] cells and the stable cell lines MR and M5R were established, respectively. Our results showed that M5R cell induced larger tumor formation compared with MR cells while these two cell lines were subcutaneously injected into SCID mice under Ha-ras overexpression conditions. It indicates that Atg5 is involved in the suppression of Ras-related tumor formation. MicroRNA (miRNA), approximately 22 nucleotide of non-coding RNA, regulates transcription and translation of the target genes and is involved in cell differentiation and tumorigenesis. A miRNA microarray (932 probes) screening was conducted to identify the autophagy-tumorigenesis-related miRNAs. Among the significant genes, miR-224 was highly expressed in autophagy deficient cell and it induced tumors. Overexpression miR-224 enhanced the activity of migration and invasion in vitro and tumor formation in vivo. In conclusion, this is the first report to demonstrate that autophagy suppresses tumor formation through down-regulation of microRNA in this case miR-224. MR and M5R cell lines were treated with IPTG for 48 hr. In addition, these cell lines were subcutaneously injected into mice to induce tumor formation. The RNA samples were extracted from above cell lines and tumors. In this research, BEL/ITRI 15K V1.0 miRNA microarray chips were used to evaluate the miRNA expression profile.
2012-06-25 | E-GEOD-38911 | biostudies-arrayexpress
Project description:Autophagy is activated in pancreatic ductal adenocarcinoma (PDAC) and is currently being considered a promising therapeutic target in clinical trials. PDAC is a highly lethal disease with incidence rate equalling mortality rate. Main reasons for PDAC lethality are late-stage diagnosis, high agressiveness and metastatic rate, lack of effective treatments as well as specific diagnostic markers. Here we show that varying levels of the Autophagy related gene 5 (Atg5) determine pancreatic tumor formation and malignancy. While homozygous deletion of Atg5 blocks tumor progression in an in vivo model of PDAC, heterozygous deletion increases tumor aggressiveness and metastasis. Further analyses reveal that monoallelic loss of Atg5 affects mitochondrial homeostasis, changes intracellular calcium oscillations, heightens extracellular cathepsin activities , and promotes a pro-tumorigenic inflammatory microenvironment collectively enhancing tumor cell migration, invasion, and metastasis. Future treatments should take into account that variations in the autophagy pathway may have opposing effects on pancreatic tumor load, especially considering the multitude of autophagy inhibitors currently tested in clinical trials.
2018-10-15 | E-MTAB-6275 | biostudies-arrayexpress
Project description:Autophagy plays an important role in physiology and tumorigenesis. We and others have demonstrated that Ha-ras overexpression induces autophagy in NIH3T3 cells. Autophagic machinery is regulated by a family of autophagy associated genes (Atg). The inducible Ha-ras oncogene was introduced into mouse embryo fibroblast Atg5 wild type [MEF-Atg5(+/+)] and Atg5 knock-out [MEF-Atg5(-/-)] cells and the stable cell lines MR and M5R were established, respectively. Our results showed that M5R cell induced larger tumor formation compared with MR cells while these two cell lines were subcutaneously injected into SCID mice under Ha-ras overexpression conditions. It indicates that Atg5 is involved in the suppression of Ras-related tumor formation. MicroRNA (miRNA), approximately 22 nucleotide of non-coding RNA, regulates transcription and translation of the target genes and is involved in cell differentiation and tumorigenesis. A miRNA microarray (932 probes) screening was conducted to identify the autophagy-tumorigenesis-related miRNAs. Among the significant genes, miR-224 was highly expressed in autophagy deficient cell and it induced tumors. Overexpression miR-224 enhanced the activity of migration and invasion in vitro and tumor formation in vivo. In conclusion, this is the first report to demonstrate that autophagy suppresses tumor formation through down-regulation of microRNA in this case miR-224.
2012-06-26 | GSE38911 | GEO
Project description:Type-I (α/β) and -II (γ) interferons (IFN), through an incompletely understood combination of redundant and unique mechanisms, are essential for host resistance to viral infection. We report a requirement for the Atg5-Atg12/Atg16L1 autophagosome elongation complex in IFNγ-mediated control of murine norovirus in macrophages. We use microarrays to compare transcriptional changes induced in control and Atg5 deficient macrophages by IFNγ treatment. Bone marrow derived macrophages were generated from Atg5flox/flox and Atg5flox/flox+LysM cre mice and treated with media alone or 100U/ml of IFNγ for 14 hrs. RNA was extracted using Trizol (Invitrogen) and 10 µg of RNA hybridized to Affymetrix microarrays.
2012-01-05 | E-GEOD-34863 | biostudies-arrayexpress
Project description:Type-I (α/β) and -II (γ) interferons (IFN), through an incompletely understood combination of redundant and unique mechanisms, are essential for host resistance to viral infection. We report a requirement for the Atg5-Atg12/Atg16L1 autophagosome elongation complex in IFNγ-mediated control of murine norovirus in macrophages. We use microarrays to compare transcriptional changes induced in control and Atg5 deficient macrophages by IFNγ treatment.
2012-01-05 | GSE34863 | GEO
Project description:In order to understand the contribution of autophagy and alternative NF-kappaB signalling to transcriptional output in A549 lung cancer cells, RNAi was used to knockdown the expression of core autophagy genes (ATG5, ULK1) or the key subunit of alternative NF-kappaB RELB. Seven samples were prepared for each biological replicate; two sequence independent non-targeting control siRNAs were transfected as a negative control. Three sequence independent siRNAs targeting the core autophagy machinery were transfected (ATG5 si, ATG5 si(2), ULK1 si). N.B. ATG5 si(2) only partially ablates Atg5 protein expression whereas ATG si has greater efficacy. Two sequence independent siRNAs targeting RELB were transfected (RELB si, RELB si(2) ). Three independent biological replicates of all conditions were obtained, by performance of the experiment on different days.
2015-09-18 | E-GEOD-73158 | biostudies-arrayexpress
Project description:Inflammation is critical for controlling infections but can cause disease when unchecked. For tuberculosis, the leading cause of death by infection, neutrophil-dominated inflammation is associated with disease progression, emphasizing the need to understand how neutrophil functions are regulated during Mycobacterium tuberculosis infection. Atg5 was the first gene shown to specifically function within neutrophils to promote control of M. tuberculosis. ATG5 is best studied for its role in autophagy, however, the protective activity of ATG5 in neutrophils was unexpectedly independent of other autophagy proteins and remained elusive. We report that ATG5 is required in neutrophils to suppress type I interferon-induced neutrophil extracellular trap (NET) release and swarming during M. tuberculosis infection. Elevated NET release contributes to the early susceptibility of Atg5fl/fl-LysM-Cre mice during infection. These findings identify ATG5 as a master regulator of how type I interferon influences neutrophil responses during infection, revealing a new potential target for host-directed therapies.
2025-03-07 | GSE280193 | GEO
Project description:Purpose: study of function of ATG5 protein on zebrafish larvae development Methods: Using morpholino oligos for atg5 gene knock down and overexpression, injected into one- to four-cell-stage embryos,extracted total RNA, then sending to RNA sequencing. Results: we compared to Wildtype, 5MO and atg5 mRNA groups, we analyza autophagy related gene mRNA expression, there are obvious different. Conclusion: our study showed the function of autophagy related gene 5 on zebrafish larvae, it has an important significant for understanding the affection of autophagy on embryo development
2019-04-30 | GSE120170 | GEO
Project description:Purpose: Global survey of the transcriptome in autophagy-deficient strains of D. discoideum Results: Our RNAseq analysis of ATG5‾, ATG5‾/12‾ and ATG5‾/12‾/16‾ cells revealed major transcriptional changes in a large number of genes in comparison to AX2 Conclusions: Our study presents a first detailed analysis of the transcriptome in autophagy-deficient strains of D. discoideum. The data were generated by RNA-seq technology. The optimised data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell. We conclude that RNA-seq based transcriptome characterisation would expedite genetic network analyses and permit the dissection of complex biologic functions.
2022-12-13 | GSE142251 | GEO
Project description:Depletion of autophagy-associated protein 5 (Atg5), specifically within the eosinophil lineage in mice, resulted in increased body weight, impaired glucose metabolism, and structural alterations in adipose tissue. Our findings highlight that Atg5 influences the functional activity of eosinophils within adipose tissue rather than their quantity. To gain a deeper understanding of the molecular mechanisms underlying ATG5's role in eosinophils, we conducted total RNA-seq analyses on control and Atg5-deficient eosinophils isolated from both bone marrow and blood of mice.
2023-11-21 | GSE245134 | GEO