Mir-30e* is an independent subtype-specific prognostic marker in breast cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE59829 | GEO | 2015/07/31
SECONDARY ACCESSION(S): PRJNA256342
REPOSITORIES: GEO
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Project description:Both gene and miRNA expression patterns separately correlate with survival in breast cancer suggesting that the development of models using both miRNAs and gene markers might improve their prediction performance. In this study miRNAs significantly associated with development of distant metastasis were identified and further investigated and validated in the publicly available dataset from the METABRIC. A combined outcome prediction model using gene expression, miRNA expression and clinico-pathological features was implemented. Fresh-frozen primary tumors were obtained from 123 patients with operable breast cancer previously untreated, pathologically defined as axillary node-negative and undergoing radical or conservative surgery at the Istituto Nazionale Tumori of Milano (INTM) between1990 and 1998. Patients were selected in order to have a comparable pattern of classical risk factors (age, tumor size).
2015-07-31 | E-GEOD-59829 | biostudies-arrayexpress
Project description:BackgroundBreast cancer clinical outcome is affected by tumor molecular features, and the identification of subtype-specific prognostic biomarkers is relevant for breast cancer translational research. Gene expression signatures proved to be able to complement prognostic information provided by classical clinico-pathological features. Recently, microRNAs (miRNAs) have been causally linked to tumorigenesis and cancer progression and have been associated with patient outcome, also in breast cancer.MethodsMicroRNAs associated with the development of distant metastasis were identified in a cohort of 92 ESR1+/ERBB2- lymph node-negative breast cancers from patients not receiving adjuvant treatment. Results were confirmed and further investigated in a total of 1246 miRNA and gene expression profiles of the Molecular Taxonomy of Breast Cancer International Consortium data set. Moderated t-test, univariable and multivariable Cox regression models were used for statistical analyses.ResultsmiR-30e* was identified as independent protective prognostic factor in lymph node-negative untreated patients with ESR1+/ERBB2- tumours and retained a significant association with a good prognosis in treated patients with the same tumor subtype as well as in the ERBB2+ subtype, but not in ESR1-/ERBB2- tumours.ConclusionsWe highlighted a relevant and subtype-specific role in breast cancer for miR-30e* and demonstrated that adding miRNA markers to gene signatures and clinico-pathological features can help for a better prognostication.
| S-EPMC4506390 | biostudies-literature
Project description:Introduction: MicroRNAs (miRNAs) are small non-coding RNA that play a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. Methods: Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant. Results: We analyzed 32 tissue samples and 108 serum samples from 8 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. The serum levels of miR-3200 declined during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates. Conclusion: Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes.
2015-10-31 | GSE70754 | GEO
Project description:Schmitz2014 - RNA triplex formation
The model is parameterized using the
parameters for gene CCDC3 from Supplementary Table S1. The two
miRNAs which form the triplex together with CCDC3 are miR-551b and
miR-138.
This model is described in the article:
Cooperative gene regulation
by microRNA pairs and their identification using a
computational workflow.
Schmitz U, Lai X, Winter F,
Wolkenhauer O, Vera J, Gupta SK.
Nucleic Acids Res. 2014 Jul; 42(12):
7539-7552
Abstract:
MicroRNAs (miRNAs) are an integral part of gene regulation
at the post-transcriptional level. Recently, it has been shown
that pairs of miRNAs can repress the translation of a target
mRNA in a cooperative manner, which leads to an enhanced
effectiveness and specificity in target repression. However, it
remains unclear which miRNA pairs can synergize and which genes
are target of cooperative miRNA regulation. In this paper, we
present a computational workflow for the prediction and
analysis of cooperating miRNAs and their mutual target genes,
which we refer to as RNA triplexes. The workflow integrates
methods of miRNA target prediction; triplex structure analysis;
molecular dynamics simulations and mathematical modeling for a
reliable prediction of functional RNA triplexes and target
repression efficiency. In a case study we analyzed the human
genome and identified several thousand targets of cooperative
gene regulation. Our results suggest that miRNA cooperativity
is a frequent mechanism for an enhanced target repression by
pairs of miRNAs facilitating distinctive and fine-tuned target
gene expression patterns. Human RNA triplexes predicted and
characterized in this study are organized in a web resource at
www.sbi.uni-rostock.de/triplexrna/.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000530.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000530 | BioModels
Project description:Introduction: MicroRNAs (miRNAs) are small non-coding RNA that play a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. Methods: Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, Spearman, Wilcoxon signed-ranks tests. Pâ¤0.05 was considered statistically significant. Results: We analyzed 32 tissue samples and 108 serum samples from 8 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. The serum levels of miR-3200 declined during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates. Conclusion: Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes. Serum and tissue from a total of 27 consecutive patients diagnosed with locally advanced breast cancer undergoing NAC treatment were collected however microarray data were generated from tissue biopsy of 5 patients at four timepoints for both Normal and tumor. Additionally 3 tissue from only tumor at four timepoints and 6 patients at two timepoint T1 and T4
2015-10-31 | E-GEOD-70754 | biostudies-arrayexpress
Project description:MicroRNA expression profiles were sucessfully contructed in 397 patients with NSCLC and 151 corresponding adjacent noncancerous tissues using a custom microarray containing probes for 1888 miRNAs and an outcome prediction of miRNA signature was successfully identified for predicting prognosis in NSCLC.
2017-08-22 | GSE53882 | GEO
Project description:Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis. In this regard, we investigated the expression pattern of selected miRNAs at the 14q32 locus in TCGA kidney tumors and in ccRCC cell lines. We validated that the miRNA cluster is downregulated in ccRCC (and cell lines) as well as in papillary kidney tumors relative to normal kidney tissues and primary renal proximal tubule epithelial (RPTEC) cells. We demonstrated that agents modulating expression of DNMT1 (e.g., 5-Aza-deoxycytidine) could modulate miRNA expression in ccRCC cell lines. Lysophosphatidic acid (LPA, a Lysophospholipid mediator elevated in ccRCC) not only increased labile iron content but also modulated expression of 14q32 miRNAs. Through an overexpression approach targeting a subset of 14q32 miRNAs (specifically at subcluster A: miR-431, miR-432, miR-127, and miR-433) in 769-P cells, we uncovered changes in cellular viability and claudin-1, a tight junction marker. A global proteomic approach was implemented using these miRNA overexpressing cell lines which uncovered ATXN2 as a highly downregulated target, which has a role in chronic kidney disease pathogenesis. Collectively, these findings support a contribution of miRNAs at 14q32 in ccRCC pathogenesis.
2023-05-10 | PXD036428 | Pride
Project description:There are many subtypes of dementia, and identification of diagnostic biomarkers that are minimally-invasive, low-cost, and efficient is desired. Circulating microRNAs (miRNAs) have recently gained attention as easily accessible and non-invasive biomarkers. We conducted a comprehensive miRNA expression analysis of serum samples from 1348 Japanese dementia patients, composed of four subtypes—Alzheimer’s disease (AD), vascular dementia, dementia with Lewy bodies (DLB), and normal pressure hydrocephalus—and 246 control subjects. We used this data to construct dementia subtype prediction models based on penalized regression models with the multiclass classification. We constructed a final prediction model using 46 miRNAs, which classified dementia patients from an independent validation set into four subtypes of dementia. Network analysis of miRNA target genes revealed important hub genes, SRC and CHD3, associated with the AD pathogenesis. Moreover, MCU and CASP3, which are known to be associated with DLB pathogenesis, were identified from our DLB-specific target genes. Our study demonstrates the potential of blood-based biomarkers for use in dementia-subtype prediction models. We believe that further investigation using larger sample sizes will contribute to the accurate classification of subtypes of dementia.
2021-10-22 | GSE167559 | GEO
Project description:MicroRNAs (miRs) are small non-coding RNAs that can function as tumor suppressor genes. We previously reported that miR-1 is among the most consistently down-regulated miRs in primary human prostate tumors. In this follow-up study, we further corroborated this finding in an independent dataset and made the novel observation that miR-1 expression is further reduced in distant metastasis and is a predictor of disease recurrence. Moreover, we performed in vitro experiments to explore the candidate tumor suppressor function of miR-1. Cell-based assays showed that miR-1 is epigenetically silenced in human prostate cancer cells. Overexpression of miR-1 in these cells led to growth inhibition and down-regulation of genes in pathways regulating cell cycle progression, mitosis, DNA replication/repair, and actin dynamics. This observation was further corroborated with protein expression analysis and 3’-UTR-based reporter assays, indicating that genes in these pathways are either direct or indirect targets of miR-1. A gene set enrichment analysis revealed that miR-1-mediated tumor suppressor effects are globally similar to those of histone deacetylase inhibitors. Lastly, we obtained preliminary evidence that miR-1 alters gH2A.X marker expression and affects the cellular organization of F-actin and filipodia formation. In conclusion, our findings indicate that miR-1 acts as a tumor suppressor in prostate cancer by influencing multiple cancer-related processes and by inhibiting cell proliferation and motility. In this study we monitored global miRNA expression changes in prostate cancer LNCaP cells treated with the epigenetic compounds 5-Azacytidine (5-AzaC) and/or trichostatin A (TSA). Cells were treated with epigenetic drugs for 36 hours and total RNA was isolated for hybridization to miRNA microarrays. 5 independent experiments were performed (n=4 for combined treatment). The candidate prostate tumor suppressor miRNAs, miR-1, miR-206, and miR-27 were up-regulated in LNCaP cells for Affymetrix microarray analysis. LNCaP cells were transfected with pre-miR oligos and 24 hr post-transfection total RNA was collected for microarray analysis; total of three independent experiments.
2011-12-01 | E-GEOD-31620 | biostudies-arrayexpress
Project description:DEAD-box RNA-binding proteins (RBPs) play a significant role in RNA metabolism to achieve cellular homeostasis, including miRNA biogenesis and transcription. Hypoxia induces stemness cell-like characteristics in cancer cells and promotes malignant progression. Despite the fact that hypoxia can induce the changes in protein and RNA modification, thereby regulating downstream gene expressions, how modifications at different molecular layers interplay with each other are poorly understood. Here we show that hypoxia induces HectH9-mediated K63-linked polyubiquitination of the DEAD-box protein DDX17 as well as reduces N6-methyladenosine (m6A) marks in pri-miRNAs. While m6A potentiates DDX17 binding to pri-miRNAs, decreased m6A modifications of pri-miRNAs and increased polyubiquitination of DDX17 under hypoxia lead to decreased DDX17 binding to pri-miRNAs binding. These events enhance the association of DDX17 with the ubiquitin receptor p300 and lead to a decrease in miRNA biogenesis, especially for miRNAs regulating stemness and stemness-related genes. In addition, polyubiquitinated DDX17 together with p300 upregulates H3K56Ac levels on the stemness and stemness-related genes, resulting in enhancement of tumor initiating ability. Post-transcriptionally, decreased miRNA production, including those targeting stemness genes or stemness-related genes, also facilitates tumor initiation. Together, hypoxia triggers DDX17 poly-ubiquitination, which orchestrates dual mechanisms to increase tumor initiating ability and promote tumor progression.
2018-03-09 | PXD006059 | JPOST Repository