Crotonylation and proteome of ovarian cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Min Li
PROVIDER: PXD068343 | iProX | Sat Sep 13 00:00:00 BST 2025
REPOSITORIES: iProX
Similar Datasets
Project description:Endometrial decidualization is essential for pregnancy. Impaired decidualization is a hallmark of preeclampsia (PE), yet the underlying mechanisms remain unclear. Herewe show that uterine pyruvate dehydrogenase E1 subunit α (PDHA1) K385 crotonylation (K385cr) is crucial in metabolic reprogramming and decidualization. In PE women, decidual PDHA1 K385cr is markedly reduced. In mice, Pdha1 K385cr deficiency causes endometrial metabolic dysregulation, poor decidualization, and a PE-like phenotype. Mechanistically, crotonylation promotes PDHA1 phosphorylation, inhibiting pyruvate dehydrogenase activity and enhancing glycolysis and NAD+ generation. In turn, NAD+ increases SIRT2-mediated FOXO1 deacetylation and nuclear translocation, upregulating decidual gene expression. In Pdha1 K385cr deficient mice, treatment of the NAD⁺ precursor β-NMN enhances the NAD⁺-SIRT2 FOXO1 pathway and decidualization, alleviating the PE-like phenotype. Our results indicate that PDHA1 K385cr is a key metabolic regulator in the pregnant uterus and that impaired PDHA1 K385cr may contribute to PE, suggesting that enhancing the NAD⁺-SIRT2-FOXO1 pathway may be exploited for PE intervention.
2026-04-27 | GSE327790 | GEO
Project description:Purpose: hsa_circ_0005505 stably knockdown cells (circ-sh1 and circ-sh2) and its corresponing control cells (con-sh) were constructed using its specific shRNAs. Next-generation sequencing (NGS) has used to examine hsa_circ_0005505 regulated transcripts. Methods: mRNA profiles of circsh1, circsh2 and con-sh were generated by deep sequencing using IlluminaI HiSeq 4000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays Results: We found 816 and 909 transcripts downregulated in circ-sh1 and circ-sh2 cells compared with con-sh cells, respectively. But 712 and 723 transcripts upregulated in circ-sh1 and circ-sh2 cells compared with con-sh cells, respectively. The differential expression with a fold change ≥1.5 and p value <0.05. Conclusions: Our study represents the first detailed analysis of hsa_circ_0005505-regulated transcripts in breast cancer cells.
2019-03-08 | GSE111665 | GEO
Project description:We report the application of Illumina paired-end RNA-seq approach for transcriptome of brain tissue in mice. By removing sequence-dependent bias and amplification noise using UMI-tools. The mapped reads of each sample were assembled using StringTie. After the final transcriptome was generated, StringTie and edgeR was used to estimate the expression levels of all transcripts. By obtaining a total of million paired-end reads of sequence from cerebral cortex tissue, we generated transcriptome profiles of mouse ischemic cortex in sham, 24 h after focal ischemia, 28 d after focal ischemia, with or without neuron-specific knockdown of TIPARP, respectively. We found 2017 differentially expressed genes (DEGs) between Sham+AAV-SYN-shRNA-Con and tMCAO+AAV-SYN-shRNA-Con group, and 516 DEGs between tMCAO+AAV-SYN-shRNA-Con and tMCAO+AAV-SYN-shRNA-TIPARP group at 24 h after stroke. In addition, we found 487 DEGs between Sham+AAV-SYN-shRNA-Con and tMCAO+AAV-SYN-shRNA-Con group, and 192 DEGs between tMCAO+AAV-SYN-shRNA-Con and tMCAO+AAV-SYN-shRNA-TIPARP group at 28 d after stroke. This study provides a detailed analysis of the underlying mechanisms of neuron-specific knockdown of TIPARP in neuronal injury and long-term effect, with biologic replicates, generated by RNA-seq technology.
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Project description:Purpose: Increasing genomics-based evidence suggests that synchronous endometrial and ovarian cancer (SEOC) represents clonally related primary and metastatic tumors. A systematic analysis of the global protein landscape of SEOCs, heretofore lacking, could reveal functional and disease-specific consequences of known genetic alterations, the directionality of metastasis, and accurate histological markers to distinguish SEOCs from single-site tumors. Experimental Design: We performed a systematic proteogenomic analysis of 29 patients diagnosed with SEOC at three international gynecologic oncology treatment centers (Chicago, Vancouver, Tübingen). For direct comparison to single-site tumors, we included 9 patients with single-site endometrioid ovarian and 26 patients with single-site endometrial endometrioid cancer. For all 64 patients, we performed sequencing of a 275-gene cancer panel combined with compartment-resolved mass spectrometry (MS) based proteomics of consecutive tissue sections to compare global (6,000+ proteins), tumor, and stromal proteomes. Results: DNA-based panel sequencing confirmed that most SEOCs are clonally related, suggesting primary and metastatic disease. These findings were further substantiated on the global proteome level, uncovering pronounced differences between SEOCs and single tumors and underscoring the importance of the stromal proteome in defining and identifying SEOCs. Our integrated proteogenomic approach confirmed that SEOCs more closely resemble endometrial endometrioid than endometrioid ovarian cancers. Conclusions: The integrated proteogenomic data show that SEOCs are distinguishable from endometrial endometrioid or endometrioid ovarian cancers. Based on their proteogenomic similarity to endometrial endometrioid cancers, we conclude that most synchronous endometrial and ovarian cancers represent primary endometrial endometrioid cancers that have metastasized to the ovary.
2025-03-11 | PXD059172 | Pride
Project description:We hypothesized that the uterine microbiome postpartum would affect the endometrial transcriptome in “real-time” (implicating a direct interaction between microbial products and the endometrium and also that the microbiome could program the future function of the endometrium (implicating a uterine programming perhaps through mechanisms similar to inflammatory memory). To test this hypothesis, we performed 16S rRNA gene sequencing of the endometrial microbiome at one, five and nine weeks after calving and tested for an effect of the microbial population on the endometrial transcriptome at five and nine weeks after calving using mRNA-sequencing. As expected, the initiation of cyclicity and elevated circulating progesterone (P4) affected the endometrial transcriptome. We also report evidence for both “real-time” and long-term programming of the endometrial transcriptome by the microbiome. An unexpected result was that some of the affected genes in the endometrial microbiome on the endometrial transcriptome were identical to those affected by ovarian cyclicity. This unexpected observation may implicate an indirect mechanism through which the endometrial microbiome can act in a systemic manner to mediate endometrial function through a pathway that involves restoration of ovarian cyclicity postpartum.
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Project description:Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive brain tumor of childhood with a poor overall survival. The salient molecular feature of ATRT is the loss of SMARCB1 which results in epigenetic dysregulation of the genome. SMARCB1 loss affects lineage commitment and differentiation by controlling gene expression. We hypothesized that additional epigenetic factors co-operate with SMARCB1 loss to control cell self-renewal and drive ATRT. We identified SIRT2 as a primary dependency in ATRT. Using a combination of RNA-seq, CUT&RUN and single RNA sequencing in model systems ATRT, we observed genome-wide reorganization of active chromatin and significantly changes in genes expression in ATRT cells with genetic (with shRNA) or chemical (with Tenovin or Thiomyristoyl (TM)) SIRT2 deactivation. Single-cell RNA transcriptome analysis of xenograft tumors revealed the elimination of tumor cells expressing stem cell genes and expansion of tumor cells expressing differentiated genes in vivo. Furthermore, SIRT2 inhibition induced apoptosis, decreased tumor growth and prolonged survival in orthotopic xenograft models. In summary we demonstrated that SIRT2 inhibition is a molecular vulnerability in SMARCB1-deleted tumors with therapeutic potential.
2025-06-16 | GSE278558 | GEO
Project description:Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive brain tumor of childhood with a poor overall survival. The salient molecular feature of ATRT is the loss of SMARCB1 which results in epigenetic dysregulation of the genome. SMARCB1 loss affects lineage commitment and differentiation by controlling gene expression. We hypothesized that additional epigenetic factors co-operate with SMARCB1 loss to control cell self-renewal and drive ATRT. We identified SIRT2 as a primary dependency in ATRT. Using a combination of RNA-seq, CUT&RUN and single RNA sequencing in model systems ATRT, we observed genome-wide reorganization of active chromatin and significantly changes in genes expression in ATRT cells with genetic (with shRNA) or chemical (with Tenovin or Thiomyristoyl (TM)) SIRT2 deactivation. Single-cell RNA transcriptome analysis of xenograft tumors revealed the elimination of tumor cells expressing stem cell genes and expansion of tumor cells expressing differentiated genes in vivo. Furthermore, SIRT2 inhibition induced apoptosis, decreased tumor growth and prolonged survival in orthotopic xenograft models. In summary we demonstrated that SIRT2 inhibition is a molecular vulnerability in SMARCB1-deleted tumors with therapeutic potential.
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Project description:Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive brain tumor of childhood with a poor overall survival. The salient molecular feature of ATRT is the loss of SMARCB1 which results in epigenetic dysregulation of the genome. SMARCB1 loss affects lineage commitment and differentiation by controlling gene expression. We hypothesized that additional epigenetic factors co-operate with SMARCB1 loss to control cell self-renewal and drive ATRT. We identified SIRT2 as a primary dependency in ATRT. Using a combination of RNA-seq, CUT&RUN and single RNA sequencing in model systems ATRT, we observed genome-wide reorganization of active chromatin and significantly changes in genes expression in ATRT cells with genetic (with shRNA) or chemical (with Tenovin or Thiomyristoyl (TM)) SIRT2 deactivation. Single-cell RNA transcriptome analysis of xenograft tumors revealed the elimination of tumor cells expressing stem cell genes and expansion of tumor cells expressing differentiated genes in vivo. Furthermore, SIRT2 inhibition induced apoptosis, decreased tumor growth and prolonged survival in orthotopic xenograft models. In summary we demonstrated that SIRT2 inhibition is a molecular vulnerability in SMARCB1-deleted tumors with therapeutic potential.
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