Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA98497 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND. Perineural invasion (PNI) is the dominant pathway for local invasion in prostate cancer. To date, only few studies have investigated the molecular differences between prostate tumors with PNI and those without it. METHODS. To evaluate the involvement of both microRNAs and protein-coding genes in PNI, we determined their genome-wide expression with a custom microRNA microarray and Affymetrix GeneChips in 50 prostate adenocarcinomas with PNI and 7 without it. In-situ hybridization and immunohistochemistry was used to validate candidate genes. RESULTS. Unsupervised classification of the 57 adenocarcinomas revealed two clusters of tumors with distinct global microRNA expression. One cluster contained all non-PNI tumors and a subgroup of PNI tumors. Significance analysis of microarray data yielded a list of microRNAs associated with PNI. At a false discovery rate (FDR) < 10%, 19 microRNAs were higher expressed in PNI tumors than in non-PNI tumors. The most differently expressed microRNA was miR-224. In-situ hybridization showed that this microRNA is expressed by perineural cancer cells. The analysis of protein-coding genes identified 34 transcripts that were differently expressed by PNI status (FDR <10%). These transcripts were down-regulated in PNI tumors. Many of those encoded metallothioneins and proteins with mitochondrial localization and involvement in cell metabolism. Consistent with the microarray data, perineural cancer cells tended to have lower metallothionein expression by immunohistochemistry than nonperineural cancer cells. CONCLUSIONS. Although preliminary, our findings suggest that alterations in microRNA expression, mitochondrial function, and cell metabolism occur at the transition from a non-invasive prostate tumor to a tumor with PNI. Keywords: Disease State analysis
2008-07-01 | GSE7055 | GEO
Project description:Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. Despite its recognized clinical impact, the molecular mechanisms underlying PNI are not well understood. In this study, we isolated perineural invasion-associated cancer-associated fibroblasts (pCAFs), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared to non-perineural invasion-associated CAFs (npCAFs). Utilizing single-cell, high-throughput sequencing, and metabolomics, we identified a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAFs-derived lactate is absorbed by tumor cells, facilitating histone H3K18 lactylation. This epigenetic modification activates the transcription of neural invasion-associated genes such as L1CAM and SLIT1, thereby driving PNI in pancreatic cancer. Further exploration of metabolic reprogramming in pCAFs revealed enhanced acetylation of the glycolytic enzyme GAPDH, correlated with increased enzymatic activity and glycolytic flux. Targeting of GAPDH and lactylation modifications significantly inhibits neural invasion in a KPC mouse model. Clinical data suggested that high levels of H3K18 lactylation correlate with severe PNI and poorer patient prognosis. Our findings provide critical insights into the role of pCAFs in the PNI of pancreatic cancer, highlighting glycolytic reprogramming and lactate-driven histone modifications as potential therapeutic targets for PDAC.
2025-03-19 | GSE290654 | GEO
Project description:Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic cancer, associated with aggressive tumor behavior and adverse patient outcomes. Despite its recognized clinical impact, the molecular mechanisms underlying PNI are not well understood. In this study, we isolated perineural invasion-associated cancer-associated fibroblasts (pCAFs), which demonstrated a markedly enhanced capacity to promote neural invasion in pancreatic cancer compared to non-perineural invasion-associated CAFs (npCAFs). Utilizing single-cell, high-throughput sequencing, and metabolomics, we identified a significant upregulation of glycolysis in pCAFs, fostering a high-lactate tumor microenvironment conducive to cancer progression. pCAFs-derived lactate is absorbed by tumor cells, facilitating histone H3K18 lactylation. This epigenetic modification activates the transcription of neural invasion-associated genes such as L1CAM and SLIT1, thereby driving PNI in pancreatic cancer. Further exploration of metabolic reprogramming in pCAFs revealed enhanced acetylation of the glycolytic enzyme GAPDH, correlated with increased enzymatic activity and glycolytic flux. Targeting of GAPDH and lactylation modifications significantly inhibits neural invasion in a KPC mouse model. Clinical data suggested that high levels of H3K18 lactylation correlate with severe PNI and poorer patient prognosis. Our findings provide critical insights into the role of pCAFs in the PNI of pancreatic cancer, highlighting glycolytic reprogramming and lactate-driven histone modifications as potential therapeutic targets for PDAC.
2025-03-05 | GSE290845 | GEO
Project description:MicroRNAs Associated with Metastatic Prostate Cancer
| PRJNA137979 | ENA
Project description:Gene expression signatures associated with Perineural Invasion in pancreatic ductal adenocarcinoma
| PRJNA397069 | ENA
Project description:Androgen receptor (AR)-negative castration-resistant prostate cancer (CRPC) is highly aggressive and resistant to current therapies. BET bromodomain protein BRD4 binds to super-enhancers (SEs) that drive high expression of oncogenes in many cancers. A BET inhibitor JQ1 has been found to suppress malignant phenotypes of prostate cancer cells, however, the target genes of JQ1 remains largely unknown. Here we show that SE-associated genes specific for AR-negative CRPC PC3 cells include the genes involved in migration and invasion and that JQ1 impairs migration and invasion of PC3 cells. We identified the long non-coding RNA MANCR, which is markedly down-regulated by JQ1 and found that BRD4 binds to the MANCR locus. MANCR knockdown led to a significant decrease in migration and invasion of PC3 cells. RNA sequencing analysis revealed that expression of the genes involved in migration and invasion is altered by MANCR knockdown. In summary, our data demonstrate that MANCR has a critical role for cellular migration and invasion abilities of PC3 cells.
2020-03-23 | GSE145081 | GEO
Project description:Approximately half of all microRNAs reside within intronic regions and are often co-transcribed with their host genes. However, most studies on intronic microRNAs focus on individual microRNAs, and conversely most studies on protein-coding and non-coding genes frequently ignore any intron-derived microRNAs. We hypothesize that the individual components of such multi-genic loci may play cooperative or competing roles in driving disease progression, and that examining the combinatorial effect of these components would uncover deeper insights into their functional importance. To address this, we perform systematic analyses of intronic microRNA:host loci in colon cancer. We observe that the FTX locus, comprising of a long non-coding RNA FTX and multiple intronic microRNAs, is highly upregulated in cancer and demonstrate that cooperativity within this multi-component locus promotes cancer growth. In addition, we show that FTX interacts with DHX9 and DICER and delineate its novel roles in regulating A-to-I RNA editing and microRNA expression. These results show for the first time that a long non-coding RNA can regulate A-to-I RNA editing, further expanding the functional repertoire of long non-coding RNAs. We further demonstrate the inhibitory effects of intronic miR-374b and -545 on the tumor suppressors PTEN and RIG-I to enhance the proto-oncogenic PI3K-AKT signaling. Finally, we show that intronic miR-421 may exert an autoregulatory effect on miR-374b and -545. Taken together, our data unveil the intricate interplay between intronic microRNAs and their host transcripts in the modulation of key signaling pathways and disease progression, adding new perspectives to the functional landscape of multi-genic loci.
2021-01-05 | PXD021823 | Pride
Project description:To investigate the mechanisms of cancer cell migration during perineural invasion in pancreatic cancer, we injected fluorescently labelled MiaPaCA-2 cells in the sciatic nerves and collected the leader and lagger cells.
2023-03-31 | GSE207319 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE26022: [Gene Expression Training Set] Protein-coding and MicroRNA Biomarkers of Recurrence of Prostate Cancer Following Radical Prostatectomy GSE26242: [Gene Expression Validation Set] Protein-coding and MicroRNA Biomarkers of Recurrence of Prostate Cancer Following Radical Prostatectomy GSE26245: [miRNA Training Set] Protein-coding and MicroRNA Biomarkers of Recurrence of Prostate Cancer Following Radical Prostatectomy GSE26247: [miRNA Validation Set] Protein-coding and MicroRNA Biomarkers of Recurrence of Prostate Cancer Following Radical Prostatectomy Refer to individual Series
2011-06-01 | E-GEOD-26367 | biostudies-arrayexpress
Project description:Pseudogenes, non-coding homologs of protein-coding genes, were once considered non-functional evolutional relics. Recent studies have shown that pseudogene transcripts can regulate their parental transcripts by sequestering shared microRNAs, thus acting as competing endogenous RNAs (ceRNAs). In this study, we utilize an unbiased screen to identify the ferritin heavy chain 1 (FTH1) transcript and multiple FTH1 pseudogenes as targets of several oncogenic miRNAs in prostate cancer. We characterize the critical role of this FTH1 gene:pseudogene:microRNA network in regulating tumorigenesis in prostate cancer, and show that impairing microRNA binding and subsequent ceRNA crosstalk results in complete phenotype rescue. Our results also demonstrate that pseudogenes are able to regulate intracellular iron levels, which are crucial for multiple physiological and pathophysiological processes. In summary, we describe a novel and extensive gene:pseudogene ceRNA network comprising multiple microRNAs and multiple pseudogenes derived from a single parental gene, which regulates iron storage and tumorigenesis in prostate cancer.
2017-07-26 | GSE101837 | GEO