Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long noncoding RNA EPCART regulates translation through PI3K/AKT/mTOR pathway and PDCD4 in prostate cancer

ABSTRACT: While hundreds of cancer-associate long noncoding RNAs (lncRNAs) have been discovered, their functional role in cancer cells is still a mystery for the majority of them. Increasing number of lncRNAs are recognized to function in the cytoplasm, including as modulators of translation. Here, we investigated the detailed molecular identity and functional role of EPCART, a lncRNA we previously discovered to be a potential oncogene in AR- and ERG-regulated prostate cancer (PCa) tumors. First, we confirmed EPCART to be a non-peptide-coding lncRNA with in silico methods and validated the transcript structure of EPCART in vitro. Pathway analysis of differentially expressed protein-coding genes in EPCART knockout cells implied EPCART to inhibit translational machinery of PCa cells. While drastic changes in the global translation were not detected in EPCART knockout cells by polysome profiling, EPCART located largely in the cytoplasm and at the sites of translation. With quantitative whole proteome studies on EPCART knockout cells we discovered PDCD4, an inhibitor of protein translation, to be increased by EPCART reduction. Further studies indicated that the inhibitory effect of EPCART on translation was mediated by reduced activation of AKT and inhibition of mTORC1 pathway. Together, our findings identify EPCART as a translation-associated lncRNA that functions via modulation of AKT/mTORC1/PDCD4 pathway in PCa cells. Furthermore, we provide evidence for prognostic potential of PDCD4 in PCa tumors in connection with EPCART.

ORGANISM(S): Homo sapiens

PROVIDER: GSE249960 | GEO | 2024/07/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

LARP1 mRNP scaffolds mTORC1 to stimulate translation initiation of an essential class of mRNAs

Project description:The RNA biding protein, LARP1, has been proposed to function downstream of mTORC1 to positively regulate the translation of 5M-bM-^@M-^YTOP mRNAs such as ribosome protein (RP) mRNAs. However, its regulatory roles in mTORC1-mediated translation remain unclear. PAR-CLIP of LARP1 revealed its direct and dynamic interactions with RP mRNAs through pyrimidine-enriched sequences in the 5M-bM-^@M-^YUTR of RP mRNAs when mTOR activity is inhibited. Importantly, this LARP1 is a direct substrate of mTORC1 and S6K1/Akt, and phosphorylated LARP1 scaffolds mTORC1 on translation-competent mRNAs to facilitate 4EBP1 and S6K1 phosphorylation. Ablation of LARP1 causes multiple defects in the processes of translation including abnormal eIF4G1 interaction with RP mRNAs and inefficient RP mRNA elongation thereby reducing ribosome biogenesis and cell proliferation. These observations illustrate that LARP1 functions both an effector and a regulator for local mTORC1 activity, and acts as a molecular switch for ribosome biogenesis by sensing growth factor/nutrient signaling. LARP1-bound RNA regions were sequenced from HEK293T cells under growing or mTOR-inactive conditions. In parallel, mRNA abundance was quantified, in biological duplicate, from HEK293T cells under the same conditions.

2014-07-31 | E-GEOD-59599 | biostudies-arrayexpress

mTORC1/2 inhibition re-sensitizes platinum-resistant ovarian cancer by disrupting selective translation of DNA damage and survival mRNAs

Project description:Using platinum-resistant OVCAR-3 cells treated with the selective mTORC1/2 inhibitor INK128/MLN128, we conducted genome-wide transcription and translation studies and analyzed the effect on cell proliferation, AKT-mTOR signaling and cell survival, to determine whether carboplatin resistance involves selective mRNA translational reprogramming, and whether it is sensitive to mTORC1/2 inhibitio.n

2018-07-31 | GSE116387 | GEO

Neuronal activity promotes nuclear proteasome-mediated degradation of PDCD4 to regulate activity-dependent transcription in neurons

Project description:Activity-dependent gene expression is critical for synapse development and plasticity. To elucidate novel mechanisms linking neuronal activity to changes in transcription, we compared the nuclear proteomes of tetrodotoxin-silenced and bicuculline-stimulated cultured neurons using nuclear-localized APEX2 proximity biotinylation and mass spectrometry. The tumor suppressor protein PDCD4 was enriched in the nuclear proteome of silenced neurons, and PDCD4 levels rapidly decreased in the nucleus and cytoplasm of stimulated neurons. The activity-dependent decrease of PDCD4 was prevented by inhibitors of both PKC and proteasome activity and by a phospho-incompetent mutation of Ser71 in the βTRCP ubiquitin ligase-binding motif of PDCD4. We compared the activity-dependent transcriptomes of neurons expressing wildtype or degradation-resistant (S71A) PDCD4. We identified 91 genes as PDCD4 targets at the transcriptional level, including genes encoding proteins critical for synapse formation, remodeling, and transmission. Our findings indicate that regulated degradation of nuclear PDCD4 facilitates activity-dependent transcription in neurons.

2020-12-15 | GSE163127 | GEO

Analysis of PDCD4 knockdown effects by high throughput sequencing of a human epithelial cell line

Project description:Purpose: examination of gene expression and translation changes in immortalized human epithelial cells (hTERT-RPE-1) induced by PDCD4 siRNA-knockdown.

2020-01-20 | GSE138533 | GEO

LARP1 mRNP scaffolds mTORC1 to stimulate translation initiation of an essential class of mRNAs

Project description:The RNA biding protein, LARP1, has been proposed to function downstream of mTORC1 to positively regulate the translation of 5’TOP mRNAs such as ribosome protein (RP) mRNAs. However, its regulatory roles in mTORC1-mediated translation remain unclear. PAR-CLIP of LARP1 revealed its direct and dynamic interactions with RP mRNAs through pyrimidine-enriched sequences in the 5’UTR of RP mRNAs when mTOR activity is inhibited. Importantly, this LARP1 is a direct substrate of mTORC1 and S6K1/Akt, and phosphorylated LARP1 scaffolds mTORC1 on translation-competent mRNAs to facilitate 4EBP1 and S6K1 phosphorylation. Ablation of LARP1 causes multiple defects in the processes of translation including abnormal eIF4G1 interaction with RP mRNAs and inefficient RP mRNA elongation thereby reducing ribosome biogenesis and cell proliferation. These observations illustrate that LARP1 functions both an effector and a regulator for local mTORC1 activity, and acts as a molecular switch for ribosome biogenesis by sensing growth factor/nutrient signaling.

2014-07-31 | GSE59599 | GEO

Identification of cellular proteins binding to the 3’UTR of Programmed Cell Death 4 mRNA

Project description:The aim of the project is to identify RNA-binding proteins (RBPs) that interact with the 3’ untranslated region (3’UTR) of the programmed cell death 4 (PDCD4) mRNA. PDCD4 is an inflammatory tumor suppressor gene. The translation of PDCD4 mRNA is regulated by multiple RBPs. The aim is to identify RBPs which are critical for regulating PDCD4 mRNA translation by binding to its 3’UTR. For this purpose, a biotinylated PDCD4 3’UTR RNA was incubated with cytoplasmic lysate from MCF7 human breast carcinoma cells and the RNA-protein complexes pulled down by streptavidin affinity chromatography. The proteins were then eluted and resolved by SDS-PAGE. One particular protein band, migrating close to 55 KDa marker was cut out and submitted for proteomic analysis by in gel digestion and mass spectrometry.

2020-12-11 | PXD017376 | Pride

Initiation Pausing of 80S Ribosome on mRNA Is Governed by 5’UTR and Responsive to mTORC1 Signaling

Project description:This SuperSeries is composed of the following subset Series: GSE25331: Initiation pausing of mRNA translation controlled by mTORC1 signaling (microarray) GSE25626: Initiation pausing of mRNA translation controlled by mTORC1 signaling (RNA-Seq) Refer to individual Series

2011-11-12 | E-GEOD-25627 | biostudies-arrayexpress

Cytoplasmic long non-coding RNAs are differentially regulated and translated during human neuronal differentiation

Project description:The expression of long non-coding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SH5Y cells. We discovered 237 cytoplasmic lncRNAs upregulated during early neuronal differentiation, 58-70% of which are associated with polysome translation complexes. Amongst these polysome associated lncRNAs, we find 45 small ORFs to be actively translated, 17 specifically upon differentiation. 15/45 of the translated lncRNA-smORFs exhibit sequence conservation within Hominidea suggesting they are under strong selective constraint in this clade. Profiling of publicly available datasets revealed that 8/45 of the translated lncRNAs are dynamically expressed during human brain development and 22/45 are associated with cancers of the central nervous system. One translated lncRNA we discovered is LINC01116, which is induced upon differentiation and contains an 87 codon smORF exhibiting increased ribosome profiling signal upon differentiation. The resulting LINC01116 peptide localises to neurites. Knockdown of LINC01116 results in a significant reduction of neurite length in differentiated cells indicating it contributes to neuronal differentiation. Our findings indicate cytoplasmic lncRNAs interact with translation complexes, are a non-canonical source of novel peptides, and contribute to neuronal function and disease. Specifically, we demonstrate a novel functional role for LINC01116 during human neuronal differentiation.

2021-07-16 | GSE166214 | GEO

Global mRNA/LncRNA expression analysis of pancreatic tumors causing type3C Diabetes Mellitus

Project description:Pancreatic tumors with small size can cause type3C Diabetes Mellitus (PCA-DM) but the mechanism is unknown. In this study we aimed at revealing the mRNA and long noncoding RNA (LncRNA) expression patterns of pancreatic tumors that triggered PCA-DM. Four pancreatic tumors from patients with PCA-DM (A1-A4), four pancreatic tumors from patients without PCA-DM (B1-B4), and four pancreatic tissues from patients with pancreatitis were individually profiled with Agilent microarrays(Arraystar Human LncRNA Array v3.0). Pancreatic tumors with PCA-DM or without PCA-DM, and pancreatic tissues of pancreatitis were individually profiled.

2014-09-06 | E-GEOD-61166 | biostudies-arrayexpress

TSC/mTORC1 mediates mTORC2/AKT1 signaling in c-MYC-induced murine hepatocarcinogenesis via centromere protein M

Project description:Activated mTORC2/AKT signaling plays a role in hepatocellular carcinoma (HCC). Research has shown that TSC/mTORC1 and FOXO1 are distinct downstream effectors of AKT signaling in liver regeneration and metabolism. However, the mechanisms by which these pathways mediate mTORC2/AKT activation in HCC are not yet fully understood. Amplification and activation of c-MYC is a key molecular event in HCC. In this study, we explored the roles of TSC/mTORC1 and FOXO1 as downstream effectors of mTORC2/AKT1 in c-MYC-induced hepatocarcinogenesis. Using various genetic approaches in mice, we found that manipulating the FOXO pathway had minimal impact on c-MYC-induced HCC. In contrast, loss of mTORC2 inhibited c-MYC-induced HCC, an effect that was completely reversed by ablating TSC2, which activated mTORC1. Additionally, we discovered that p70/RPS6 and 4EBP1/eIF4E act downstream of mTORC1, regulating distinct molecular pathways. Notably, the 4EBP1/eIF4E cascade is crucial for cell proliferation and glycolysis in c-MYC-induced HCC. We also identified centromere protein M (CENPM) as a downstream target of the TSC2/mTORC1 pathway in c-MYC-driven hepatocarcinogenesis, and its ablation entirely inhibited c-MYC-dependent HCC formation. Our findings demonstrate that the TSC/mTORC1/CENPM pathway, rather than the FOXO cascade, is the primary signaling pathway regulating c-MYC-driven hepatocarcinogenesis. Targeting CENPM holds therapeutic potential for treating c-MYC-driven HCC.

2024-09-15 | GSE276215 | GEO

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