TDP-43 regulates cancer-associated microRNAs
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE85065 | GEO | 2016/08/02
SECONDARY ACCESSION(S): PRJNA336050
REPOSITORIES: GEO
Similar Datasets
Project description:MicroRNAs (miRNAs) play important roles in a wide range of cellular processes. Aberrant regulation of miRNA genes contributes to human diseases, including cancer. The TAR DNA binding protein 43 (TDP-43), a DNA/RNA binding protein associated with neurodegeneration, is involved in miRNA biogenesis. Here, we systematically examined miRNAs whose expression levels are regulated by TDP-43 using RNA-Seq coupled with siRNA-mediated knockdown approach. TDP-43 knocking down affected the expression of a number of miRNAs. Alterations in isomiR patterns and miRNA arm selection after TDP-43 knockdown suggest a role of TDP-43 in miRNA editing. We examined correlation of selected TDP-43 associated miRNAs and their candidate target genes in human cancers. Our data reveal highly complex roles of TDP-43 in regulating different miRNAs and their target genes. Our results suggest that TDP-43 may promote migration of lung cancer cells by regulating miR-423-3p expression. On the other hand, TDP-43 increases miR-500a-3p expression and binds to the mature miR-500a-3p sequence. Low expression of miR-500a-3p was associated with poor survival of lung cancer patients, suggesting that TDP-43 may have a suppressive role in cancer by regulating miR-500a-3p. Our experiments reveal that cancer-associated genes LIF and PAPPA may be targets of miR-500a-3p. Together with other studies, our work suggests that TDP-43-regulated miRNAs may play multi-facet roles in the pathogenesis of cancer. small RNA seq in SH-SY-5Y, SNB-19 and HT22 (TDP-43 siRNA VS Control siRNA)
2016-08-02 | E-GEOD-85065 | biostudies-arrayexpress
Project description:Cancer cachexia is a multifactorial metabolic syndrome defined by the rapid loss of skeletal muscle mass and the loss of fat mass. Up 80% of cancer patients at the late stage with cachexia suffer from progressive atrophy of adipose tissue. Unlike studies on skeletal muscle wasting, there is limited research on fat loss in cachexia. It was noted that most patients suffer from fat loss as cancer progress. Fat loss precedes muscle loss, is associated with shorter survival, and is variable to timing and intensity in various cancer populations. Increased lipolysis may be the leading cause of fat loss in cancer cachexia. miRNAs are a class of non-coding RNAs of 19~25 nucleotides that regulate gene silencing by interacting with the 3’ untranslated region (UTR) of target mRNA to cause mRNA degradation and translational repression. miRNAs play multifaceted roles in pancreatic cancer proliferation, survival, metastasis, and chemoresistance. Aberrant expression of miRNA in circulating exosomes may play potential roles in modulating fat loss in cancer cachexia. We identified 2 miRNAs, miR-16 and miR-29, which have 2-fold higher expression existed in at PDAC cells. To explore which genes in adipogenesis and lipolysis were directly affected by miR-16-5p or/and miR-29a-3p, we analyzed the targets which were down-regulated in both miR-16-5p and miR-29a-3p-transfected 3T3-L1 cells by mass analysis.
2024-06-13 | PXD037998 | Pride
Project description:Cancer cachexia is a multifactorial metabolic syndrome defined by the rapid loss of skeletal muscle mass and the loss of fat mass. Up 80% of cancer patients at the late stage with cachexia suffer from progressive atrophy of adipose tissue. Unlike studies on skeletal muscle wasting, there is limited research on fat loss in cachexia. It was noted that most patients suffer from fat loss as cancer progress. Fat loss precedes muscle loss, is associated with shorter survival, and is variable to timing and intensity in various cancer populations. Increased lipolysis may be the leading cause of fat loss in cancer cachexia. miRNAs are a class of non-coding RNAs of 19~25 nucleotides that regulate gene silencing by interacting with the 3’ untranslated region (UTR) of target mRNA to cause mRNA degradation and translational repression. miRNAs play multifaceted roles in pancreatic cancer proliferation, survival, metastasis, and chemoresistance. Aberrant expression of miRNA in circulating exosomes may play potential roles in modulating fat loss in cancer cachexia. We identified 2 miRNAs, miR-16 and miR-29, which have 2-fold higher expression existed in at PDAC cells. To explore which genes in adipogenesis and lipolysis were directly affected by miR-16-5p or/and miR-29a-3p, we analyzed the targets which were down-regulated in both miR-16-5p and miR-29a-3p-transfected 3T3-L1 cells by mass analysis.
2024-06-13 | PXD037862 | Pride
Project description:MiRNAs have been shown to alter both protein expression and secretion in different cellular contexts. By combining in vitro, in vivo and in silico techniques, we demonstrated that overexpression of pre-miR-1307 reduced the ability of breast cancer cells to induce endothelial cell sprouting and angiogenesis. However, the molecular mechanism behind this and the effect of the individual mature miRNAs derived from pre-miR-1307 on protein secretion and is largely unknown. Here, we overexpressed miR-1307-3p|0, -3p|1 and 5p|0 in MDA-MB-231 breast cancer cells and assessed the impact of miRNA overexpression on protein secretion by Mass Spectrometry. Unsupervised hierarchical clustering revealed a distinct phenotype induced by overexpression of miR-1307-5p|0 compared to the controls and to the 5’isomiRs derived from the 3p-arm. Together, our results suggest different impacts of miR-1307-3p and miR-1307-5p on protein secretion which is in line with our in vitro observation that miR-1307-5p, but not the isomiRs derived from the 3p-arm reduce endothelial cell sprouting in vitro. Hence these data support the hypothesis that miR-1307-5p is at least partly responsible for impaired vasculature in tumors overexpressing pre-miR-1307.
2024-12-11 | PXD041087 | Pride
Project description:MiRNAs regulate posttranscriptional gene expression and are widely implicated in the pathogenesis of complex diseases. We aim to elucidate miRNA regulation of the atrial mRNA signatures that associate with AF. This may provide novel mechanistical insights and candidate targets for therapies using miRNA mimics or antimiRs.
We present combined miRNAs-mRNAs sequencing in atrial tissues of patient without AF (n=22), with paroxysmal AF (n=22) and with persistent AF (n=20). MiRNA and mRNA signatures followed an ordinal scale from nonAF to paroxysmal to persistent AF patients. The previously reported mRNA sequencing identified 5228 differentially expressed genes involved in epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving collagens, glycoproteins and proteoglycans. We discovered 103 differentially expressed miRNAs. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. The expression levels of differentially expressed miRNAs were negatively correlated with the expression levels of their predicted target mRNAs. The downregulated miRNAs demonstrated a more profound transcriptome effect than the upregulated miRNAs. Upregulated biological processes enriched in miRNAs targets related to epithelial and endothelial cell migration and glycosaminoglycan biosynthesis, in line with the processes discovered by the mRNA sequencing analysis.
Combined analysis of miRNA and mRNA sequencing uncovered miRNAs with a broad transcriptional effect in human AF. Epithelial to mesenchymal transition and endothelial cell proliferation were processes controlled by downregulated miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p, which in turn may contribute to (myo)fibroblast activation and structural remodeling.\
| EGAS00001005296 | EGA
Project description:iPSC-derived neurons were treated with mimics and inhibitors of the miRNAs miR-150-5p, hsa-mir-193a-3p and hsa-miR-19b-3p.
RNA-sequencing was then performed to examine the effects of miRNA up-regulation and inhibition.
| EGAD00001006844 | EGA
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir1_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Nature Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110000.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2017-09-26 | MODEL1704110000 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mir181_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110001.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2017-09-26 | MODEL1704110001 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle regeneration during ageing (Mir378_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110002.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2017-09-26 | MODEL1704110002 | BioModels
Project description:Proctor2017 - Identifying microRNA for muscle
regeneration during ageing (Mir143_in_muscle)
This model is described in the article:
Using computer simulation
models to investigate the most promising microRNAs to improve
muscle regeneration during ageing
Carole J. Proctor & Katarzyna
Goljanek-Whysall
Scientific Reports
Abstract:
MicroRNAs (miRNAs) regulate gene expression through
interactions with target sites within mRNAs, leading to
enhanced degradation of the mRNA or inhibition of translation.
Skeletal muscle expresses many different miRNAs with important
roles in adulthood myogenesis (regeneration) and myofibre
hypertrophy and atrophy, processes associated with muscle
ageing. However, the large number of miRNAs and their targets
mean that a complex network of pathways exists, making it
difficult to predict the effect of selected miRNAs on
age-related muscle wasting. Computational modelling has the
potential to aid this process as it is possible to combine
models of individual miRNA:target interactions to form an
integrated network. As yet, no models of these interactions in
muscle exist. We created the first model of miRNA:target
interactions in myogenesis based on experimental evidence of
individual miRNAs which were next validated and used to make
testable predictions. Our model confirms that miRNAs regulate
key interactions during myogenesis and can act by promoting the
switch between quiescent/proliferating/differentiating
myoblasts and by maintaining the differentiation process. We
propose that a threshold level of miR-1 acts in the initial
switch to differentiation, with miR-181 keeping the switch on
and miR-378 maintaining the differentiation and miR-143
inhibiting myogenesis.
This model is hosted on
BioModels Database
and identified by:
MODEL1704110003.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
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.
2017-09-26 | MODEL1704110003 | BioModels