Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1153127 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30424671_1.fastq.gz | Fastqsanger.gz | |||
| SRR30424671_2.fastq.gz | Fastqsanger.gz | |||
| SRR30424672_1.fastq.gz | Fastqsanger.gz | |||
| SRR30424672_2.fastq.gz | Fastqsanger.gz | |||
| SRR30424673_1.fastq.gz | Fastqsanger.gz |
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Project description:Using engineered initiator tRNA for precise control of protein translation within cells has great promise within future orthogonal translation systems to decouple housekeeping protein metabolism from that of engineered genetic systems. Previously, E. coli strain C321.ΔA.exp lacking all UAG stop codons was created, freeing this ‘amber’ stop codon for other purposes. An engineered ‘amber initiator’ that activates translation at UAG codons is available, but little is known about amino acid it assigns to the amber start codon. Here, we combine for the first time the amber initiator tRNA in C321.ΔA.exp and measure its cellular effects. Using, targeted proteomics, we found that the amber initiator tRNA initiates proteins exclusively with methionine.
2019-03-15 | PXD012390 | panorama
Project description:The essential amino acid methionine plays a pivotal role in one-carbon metabolism, facilitating the production of S-adenosylmethionine (SAMe), a critical supplier for DNA methylation. Here we find the disruption of methionine metabolism by rapid SAMe depletion in skeletal muscle in cancer cachexia, leading to endoplasmic reticulum (ER) stress and the overexpression of regulated in development and DNA damage responses (REDD1). Targeting the DNA methylation process via DNA methyltransferases (DNMTs) and REDD1 knockout can alleviate cancer cachexia-induced skeletal muscle atrophy. Methionine supplementation maintains the DNA methylation of DNA damage-inducible transcript 4 (Ddit4) by DNMT3A, thereby inhibiting activating transcription factor 4 (ATF4)-mediated Ddit4 transcription. Our study suggests that methionine or SAMe supplementation can effectively reverse muscle atrophy in cancer cachexia, providing valuable mechanistic insights and a promising therapeutic strategy for clinical application.
2024-10-11 | GSE275001 | GEO
Project description:Translation is an essential process for all living cell types, and translation dysregulation is a common feature in cancer cells that maintain the malignacy. tRNA-iMet is essential for initiation of translation, and tRNA-iMet was considered a cancer-promoting molecular factor, as elevated tRNA-iMet levels could enhance the vigorous translation and acceralate growth of cancers. Currently, the mainstream strategies of targeting therapies for cancer theatment are to target specific alterations of oncogenes or oncoproteins invoved in certain cancer pathways, however, the adquired resistance to these treatments seem to be inevitable. There is few research explored what happens if further elevate the expression of oncogenes, based on the philosophy saying ”No Extreme will Hold Long”. In this study, we exhibite that overexpression of tRNA-iMet could inhibite growth of multiple types of cancers via energy depletion. This stratege proposed by this study displays a potential and promising option of cancer treatmen for clinical translation.
2024-08-28 | PXD055419 |
Project description:Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment. Using the pediatric brain tumor ependymoma (EPN) as a model, we found that inhibition of histone serotonylation blocks EPN tumorigenesis and regulates expression of a core set of developmental transcription factors (TFs). High-throughput, in vivo screening of these TFs revealed that ETV5 promotes EPN tumorigenesis and functions by enhancing repressive chromatin states. Neuropeptide Y (NPY) is amongst the genes repressed by ETV5 and its overexpression suppresses EPN tumor progression and tumor-associated network hyperactivity via synaptic remodeling. Collectively, these studies identify histone serotonylation as a key driver of EPN tumorigenesis, while further revealing how neuronal signaling, neuro-epigenomics, and developmental programs are intertwined to drive malignancy in brain cancer.
2024-09-09 | PXD048170 | Pride
Project description:The tRNA N7-methylguanosine (m7G) modification is not essential for yeast growth, but in mammals mis-regulations of tRNA m7G modification cause stem cell defect and developmental disorders. Here we found that tRNA m7G methyltransferase complex components METTL1 and WDR4 are elevated in lung cancer tissues and associated with poor lung cancer prognosis. Functionally, depletion of METTL1 or WDR4 suppresses proliferation, migration, and invasion of lung cancer cells. In addition, forced expression of METTL1 or WDR4 promotes lung cancer progression depending on the tRNA m7G methyltransferase activity. Mechanistically, METTL1 knockdown leads to reduced tRNA m7G modification and decreased expression of m7G-modified tRNAs. Depletion of METTL1 selectively reduces the translation of a subset of oncogenic transcripts, including the genes related to cell proliferation in a m7G related codon dependent manner. Our study uncovered a new layer of translation regulation mechanism mediated by tRNA m7G modification, provided strong evidence to support the important physiological function of mis-regulated tRNA modification in cancer, and suggested that targeting METTL1 could be a promising strategy for lung cancer treatment.
2022-12-31 | GSE173760 | GEO
Project description:The tRNA N7-methylguanosine (m7G) modification is not essential for yeast growth, but in mammals mis-regulations of tRNA m7G modification cause stem cell defect and developmental disorders. Here we found that tRNA m7G methyltransferase complex components METTL1 and WDR4 are elevated in lung cancer tissues and associated with poor lung cancer prognosis. Functionally, depletion of METTL1 or WDR4 suppresses proliferation, migration, and invasion of lung cancer cells. In addition, forced expression of METTL1 or WDR4 promotes lung cancer progression depending on the tRNA m7G methyltransferase activity. Mechanistically, METTL1 knockdown leads to reduced tRNA m7G modification and decreased expression of m7G-modified tRNAs. Depletion of METTL1 selectively reduces the translation of a subset of oncogenic transcripts, including the genes related to cell proliferation in a m7G related codon dependent manner. Our study uncovered a new layer of translation regulation mechanism mediated by tRNA m7G modification, provided strong evidence to support the important physiological function of mis-regulated tRNA modification in cancer, and suggested that targeting METTL1 could be a promising strategy for lung cancer treatment.
2022-12-31 | GSE173750 | GEO
Project description:Within a cell, protein-bound methionines can be oxidized by reactive oxygen species (ROS) or monooxygenases, and subsequently reduced by methionine sulfoxide reductases (Msrs). Methionine oxidation can result in structural damage or be the basis of functional regulation of enzymes. In addition to participating in redox reactions, methionines play an important role as the initial residue of translated proteins where they are commonly modified at their α-amine group by formylation or acetylation. Here, we investigated how formylation and acetylation of initiator methionines impact their propensity for oxidation and reduction. We show that in vitro, N-terminal methionine residues are particularly prone to chemical oxidation, and that their modification by formylation or acetylation greatly enhances their subsequent enzymatic reduction by MsrA and MsrB. Concordantly, in vivo ablation of methionyl-tRNA formyltransferase (MTF) in E. coli increases the prevalence of oxidized methionines within synthesized proteins. We show that oxidation of formylated initiator methionines is detrimental in part because it obstructs their ensuing de-formylation by peptide deformylase (PDF) and hydrolysis by methionyl aminopeptidase (MAP). Thus, by facilitating their reduction, formylation mitigates the misprocessing of oxidized initiator methionines.
2024-11-06 | PXD048776 | Pride
Project description:Tumors require ample protein synthesis to grow, and aminoacyl-tRNA synthetases, as critical translation factors, are expected to support cancer progression. Unexpectedly, overexpression of seryl-tRNA synthetase (SerRS) suppresses primary tumor growth of breast cancer. However, the effects of SerRS on metastasis have not been studied. We observe a decrease in SerRS expression in breast cancer patient metastases compared to matched primary tumors, suggesting an inhibitory role of SerRS in metastasis. Through mouse metastasis models using breast cancer cell lines overexpressing SerRS, we show that SerRS impedes both primary tumor growth and establishment of metastases. By inducing SerRS overexpression after primary tumor implantation, we demonstrate the potential of SerRS as an anticancer therapeutic. Through tumor RNA-Seq, we identify Wnt signaling among the top SerRS-regulated pathways. Using cell-based studies, we confirm SerRS suppresses Wnt signaling and metastatic processes in breast cancer cells. To our knowledge, this is the first study to show a translation factor can act as both a tumor and metastasis suppressor.
2025-02-19 | GSE264557 | GEO
Project description:De novo lipogenesis is activated in most cancers. Several lipogenic enzymes are implicated in oncogenesis and represent potential cancer therapeutic targets. RNA interference-mediated depletion of ATP citrate lyase (ACLY), the enzyme that catalyzes the first step of de novo lipogenesis, leads to growth suppression in a subset of human cancer cells. Here we demonstrate the molecular basis and potential biomarkers for ACLY-targeting therapy. First, suppression of cancer cell growth by ACLY depletion involves down-regulation of fatty acid elongase ELOVL6 at the transcriptional level. Lipid profiling revealed that ACLY depletion alters fatty acid composition in triglyceride; increased palmitate and decreased longer fatty acids, in accordance with ELOVL6 down-regulation. Second, ACLY depletion increases reactive oxygen species (ROS), whereas addition of antioxidant reduces ROS and attenuates the growth suppression. Third, ACLY depletion or ROS stimulation induce phosphorylation of AMP-activated protein kinase (AMPK), a sensor of energy and lipid metabolism. Analysis of various cancer cell lines revealed that the levels of AMPK phosphorylation (p-AMPK) correlate with the basal ROS levels, and that cancer cells with low basal p-AMPK (i.e., low basal ROS) levels are highly susceptible to ACLY depletion-mediated growth suppression. Finally, in clinical colon cancer tissues, p-AMPK levels are significantly decreased in aggressive tumors and correlate with the levels of 8-hydroxydeoxyguanosine, a hallmark of ROS stimulation. Together, these data suggest that ACLY inhibition suppresses cancer growth via palmitate-mediated lipotoxicity, and p-AMPK could be a predictive biomarker for its therapeutic outcome. Two cell lines are treated with ACLY siRNA. The samples include controls of each cell line.
2014-04-13 | E-GEOD-37243 | biostudies-arrayexpress
Project description:IL13Rα2 overexpression promotes metastasis of basal-like breast cancers IL13Rα2 depletion in highly metastatic breast cancer cells suppresses lung metastases formation by upregulating TP63 and decreasing their migratory potential
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