Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Detection of novel fusion transcriptVTI1A-CFAP46 in HHC by RNA-seq

ABSTRACT: HCC is now the second-highest cause of cancer death worldwide. Recent studies have discovered a wide range of somatic mutations in HCC. These mutations involve various vital signaling pathways, such as: Wnt/β-Catenin, p53, telomerase reverse transcriptase (TERT), chromatin remodeling, RAS/MAPK signaling, and oxidative stress. However, fusion transcripts have not been explored in HCC. To identify novel fusion transcript in HCC, in the first phase of our study, we performed targeted RNA sequencing on 6 patients with the diagnosis of HCC who underwent liver transplant (from HCC and paired non-HCC tissues). As a result of these studies, we discovered the novel fusion transcript, VTI1A-CFAP46. In the second phase of the study, we measured the expression of wild-type VTI1A in total of 21 HCC specimens (additional 13 patients) showing that 10 of 21 had up-regulation of wild-type VTI1A. VTI1A (Vesicle Transport via Interaction with t-SNARE homolog 1A) is a member of the Soluble N-ethylmaleimide-Sensitive Factor (NSF) attachment protein receptor (SNARE), which is essential for membrane trafficking and function in endocytosis, autophagy, and Golgi transport. Notably, it is known that autophagy is involved in HCC. The link between this alteration and autophagy as a potential therapeutic target in HCC patients deserves further investigation. Moreover, this study shows that fusion transcripts are worthy of additional exploration in HCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE105090 | GEO | 2020/10/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

IP-MS of human YKT6 upon mutation of possible ULK1-phosphorylation sites

Project description:Autophagy is a catabolic process during which cytosolic material is enwrapped in a newly formed double membrane structure called the autophagosome, and subsequently targeted for degradation in the lytic compartment of the cell. The fusion of autophagosomes with the lytic compartment is a tightly regulated step and involves membrane-bound SNARE proteins. These play a crucial role as they promote lipid mixing and fusion of the opposing membranes. Among the SNARE proteins implicated in autophagy, the essential SNARE protein YKT6 is the only evolutionary conserved SNARE protein from yeast to human. Alterations in YKT6 function, in both mammalian cells and nematodes, produces early and late autophagy defects that result in reduced survival. Moreover, mammalian autophagosomal YKT6 is phospho-regulated by the ULK1 kinase, preventing premature bundling with the lysosomal SNARE proteins and autophagosome-lysosome fusion. Together, our findings reveal that timely regulation of theYKT6 phosphostatus is crucial throughout autophagy progression and cell survival.

2023-03-02 | PXD038148 | Pride

NUPR1 maintains autolysosomal efflux by activating SNAP25 transcription in cancer cells

Project description:In the advanced stages of cancer, autophagy is thought to promote tumor progression through its ability to mitigate various cellular stresses. However, the details of how autophagy is homeostatically regulated in such tumors are unknown. Here, we report that NUPR1 (nuclear protein 1, transcriptional regulator), a transcriptional coregulator, is aberrantly expressed in a subset of cancer cells and predicts low overall survival rates for lung cancer patients. NUPR1 regulates the late stages of autolysosome processing through the induction of the SNARE protein SNAP25, which forms a complex with the lysosomal SNARE associated protein VAMP8. NUPR1 depletion deregulates autophagic flux and impairs autolysosomal clearance, inducing massive cytoplasmic vacuolization and premature senescence in vitro and tumor suppression in vivo. Collectively, our data show that NUPR1 is a potent regulator of autolysosomal dynamics and is required for the progression of some epithelial cancers.

2016-06-05 | GSE68873 | GEO

Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression

Project description:Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has a poor prognosis. Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) encodes a fusion protein consisting of ubiquitin and ribosomal protein L40. However, few studies have explored the effects of UBA52 on HCC. In the study, we found that UBA52 is related to autophagy by the bioinformatic analysis. High‐throughput RNA‐sequencingwas used to identifydownstreamtargetgenesof EMC6. Our results suggested that UBA52 may be a new target for the prevention or treatment of HCC.

2024-03-13 | GSE235017 | GEO

Transcriptome profiles of Snap29 knockout and wild-type mouse embryonic stem cells by RNA-seq analysis

Project description:Embryonic stem cells have the characteristics of self-renewal and pluripotent differentiation, and have broad application prospects in clinical practice. With the deepening of the research process, ESCs are expected to become the source of donor cells for regenerative medicine and cellular agriculture. Autophagy is a highly conserved catabolic process mediated by lysosomes in eukaryotic cells to meet cellular demands for metabolites and energy. Autophagy is a key process in maintaining cellular homeostasis by removing misfolded or aggregation-prone proteins and damaged organelles. Previous studies have reported that ATG3, ULK1, and other key factors in the formation stage of autophagosomes play a crucial role in maintaining the pluripotency of mouse embryonic stem cells. However, there are few reports on the regulation and molecular mechanism of SNARE proteins that mediate autophagosome-lysosome fusion, including Vamp8, Stx17, and Snap29, on the pluripotency of mESCs. The role of the SNARE protein Snap29 in regulating the self-renewal and pluripotent differentiation ability of mESC remains elusive. To better understand transcriptional landscape and signal transductions, we performed RNA-seq analysis of Snap29 knockout (KO) and wild-type (WT) mESCs at undifferentiated state and mESCs-derived-cells of differentiation .

2023-01-12 | GSE206440 | GEO

Syntaxin5’s flexibility in SNARE pairing supports Golgi functions

Project description:The intracellular transport system is an evolutionally conserved, essential, and highly regulated network of organelles and small transport carriers that traffic protein and lipid cargoes within the cell. The Conserved Oligomeric Golgi (COG) complex is the major Golgi Multisubunit Tethering Complex. Its key function is orchestration of SNARE mediated fusion of cargo carriers at the Golgi. We hypothesized the depletion of the major Golgi SNAREs GS28 (GOSR1) and GS15 (BET1L) due to COG malfunction is the major contributor to COG-related glycosylation defects. To test this, we created single, double and triple knockouts (KO) of Golgi SNAREs in HEK293T cells and analyzed the resulting mutants using a comprehensive set of biochemical, mass-spectrometry (MS) and microscopy approaches. Deletion of GS28 significantly affected GS15, but not the other two partners, STX5 and YKT6. Surprisingly, our analysis revealed that COG dysfunction is more deleterious for Golgi function than disrupting the canonical Golgi SNARE complex indicating the existence of an adaption mechanism. Indeed, quantitative mass-spectrometry analysis of STX5-interacting proteins revealed unexpected flexibility in Golgi SNARE pairing in mammalian cells. We uncovered two novel non-canonical Golgi SNARE complexes – STX5/SNAP29/VAMP7 and STX5/VTI1B/GS15/YKT6 which were increased in GS28 KO cells. Upon GS28 deletion, SNAP29 remarkably localized to the Golgi. Merely mislocalizing STX5 from Golgi abolished the SNARE substitution causing dramatic glycosylation defects. Our data points to the remarkable plasticity in the intra-Golgi membrane fusion machinery and places STX5 as the only essential Golgi Qa-SNARE.

2023-06-26 | PXD036741 | Pride

Anti-miR-21 Suppresses Hepatocellular Carcinoma Growth via Broad Transcriptional Network De-regulation

Project description:Hepatocellular carcinoma (HCC) remains a significant clinical challenge with few therapeutic options available to cancer patients. MicroRNA 21-5p (miR-21) has been shown to be upregulated in HCC, but the contribution of this oncomiR to the maintenance of tumorigenic phenotype in liver cancer remains poorly understood. We have developed potent and specific single-stranded oligonucleotide inhibitors of miR-21 (anti-miRs) and used them to interrogate dependency on miR-21 in a panel of liver cancer cell lines. Treatment with anti-miR-21, but not with a mismatch control anti-miR, resulted in significant de-repression of direct targets of miR-21 and led to loss of viability in the majority of HCC cell lines tested. Robust induction of caspase activity, apoptosis and necrosis was noted in anti-miR-21 treated HCC cells. Furthermore, ablation of miR-21 activity resulted in inhibition of HCC cell migration and suppression of clonogenic growth. To better understand the consequences of miR-21

2015-03-24 | GSE65892 | GEO

Identification of responsible genes of HCC after sustained virological response to hepatitis C virus

Project description:Risk of hepatocellular carcinoma (HCC) remains after sustained virological response (SVR) in patients with chronic hepatitis C (CHC). Epigenetic abnormalities might be key regulators in the development of HCC. This study aimed to identify the genes involved in hepatocarcinogenesis after SVR. DNA methylation in liver tissues was compared between 21 CHC patients without HCC and 28 CHC patients with HCC, all of whom had achieved SVR. Through additional comparisons with 23 CHC patients before treatment and 10 normal livers, we found that the several genes were methylated and demethylated by HCV infection and the development of HCC after achieving SVR.

2023-08-09 | GSE211345 | GEO

Tomosyn is upregulated by IgE and functions as a PKC-regulated fusion clamp in mast cell degranulation

Project description:The regulation of soluble N ethylmaleimide sensitive factor attachment receptor (SNARE) mediated membrane fusion by upstream signaling events is poorly understood. Here we show that the SNARE binding protein tomosyn-1 negatively regulates type I IgE Fc receptor (FcRI) induced degranulation of mast cells. After FcRI stimulation, tomosyn-1 (also STXBP5) was phosphorylated on serine and threonine residues and dissociated from the SNARE protein syntaxin 4 (STX4), followed by association with syntaxin 3 (STX3). Protein kinase A (PKA) and protein kinase C (PKC) prevented these activities. We identified PKC as the major kinase required for tomosyn-1 threonine phosphorylation and for the regulation of the interaction with STXs. Incubation with high IgE concentrations induced tomosyn-1 expression in cultured mast cells. In basophils from allergic patients with normal total IgE serum titers tomosyn-1 expression was lower than in patients with high IgE titers who expressed tomosyn-1 to the same extent as non-allergic subjects. Our findings identified tomosyn-1 as a negative regulator of mast cell degranulation that required PKC to switch its interaction with STX partners during fusion. The IgE-mediated upregulation of tomosyn-1 in allergic patients may represent a counter-regulatory mechanism to limit disease development.

2018-07-04 | PXD010047 | Pride

Cellular, molecular and proteomic characteristics of early Hepatocellular carcinoma

Project description:Ηepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Early de-tection/diagnosis is vital for the prognosis of HCC whereas diagnosis at late stages is associated with very low survival rate. Early diagnosis is based on patient’s 6 month surveillance and use of at least two imaging modalities. The aim of this study was to investigate diagnostic markers for the detection of early HCC based on proteome analysis, microRNAs (miRNAs) and circulat-ing tumor cells (CTCs) in the blood of patients with cirrhosis, early and advanced HCC. We studied 89 patients with HCC of whom 33 had early HCC and 28 cirrhotic patients. CTCs were detected by Real-Time Quantitative Reverse Transcription PCR and immunofluorescence using the markers Epithelial cell adhesion molecule (EPCAM), Vimentin, A Fetoprotein (AFP) and surface major Vault protein (sMVP). Expression of the five most commonly HCC-involved miRNAs (miR-122, miR-200a, miR-200b, miR-221, miR-222) was examined in the serum by qRT-PCR. Finally patient serum was analyzed by whole proteome analysis (LC/MS). Twenty seven out of 53 (51%) patients with advanced HCC had detectable CTCs. Among them, 10/27 (37%) presented evidence of mesenchymal or intermediate stage cells (vimentin and/or sMVP positive). Moreover, 5/17 (29%) patients with early HCC and 6/28 (21%) cirrhotic patients had detectable CTCs. Patients with early and advanced HCC exhibited a significant increase of miR-200b when compared to cirrhotic patients. Our proteome analysis indicated that early HCC patients present a significant upregulation of APOA2, APOC3 proteins when compared to cir-rhotic patients, that when used in combination, cover the 100% of the patients with early HCC. In conclusion, miR-200b, APOA2 and APOC3 proteins are sensitive markers and can be poten-tially useful in combination for the early diagnosis of HCC.

2023-03-11 | PXD033306 | Pride

Mass Spectrometry Uncovers Protein Interactions and Stoichiometry of Intermediates and Sub-complexes for SNARE Complex Assembly

Project description:The neuronal SNARE complex assembles from vesicular Synaptobrevin-2 as well as Syntaxin-1 and SNAP25 anchored to the presynaptic membrane. It mediates fusion of synaptic vesicles with the presynaptic plasma membrane resulting in exocytosis of neurotransmitters into the synaptic cleft. While the general sequence of SNARE complex formation is well-established, our knowledge on possible intermediates is still incomplete. We, therefore, follow the step-wise assembly of the SNARE complex and target individual SNAREs, binary sub-complexes, the ternary SNARE complex as well as interactions with Complexin-1. Using native mass spectrometry, we identify the stoichiometry of preferred sub-complexes and monitor oligomerisation of various assemblies. Importantly, we find that interactions with Complexin-1 reduce self-association of the ternary SNARE complex. Chemical cross-linking provides detailed insights into these interactions suggesting a role during membrane fusion. Taken together, we unravel possible intermediates and preferred sub-complexes and compile a road map of SNARE complex assembly including regulation by Complexin-1.

2023-01-25 | PXD030619 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data