46 research outputs found
miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells
Glioblastoma multiforme (GBM) is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells.status: publishe
Decoding the Effect of Isobaric Substitutions on Identifying Missing Proteins and Variant Peptides in Human Proteome
To
confirm the existence of missing proteins, we need to identify
at least two unique peptides with length of 9–40 amino acids
of a missing protein in bottom-up mass-spectrometry-based proteomic
experiments. However, an identified unique peptide of the missing
protein, even identified with high level of confidence, could possibly
coincide with a peptide of a commonly observed protein due to isobaric
substitutions, mass modifications, alternative splice isoforms, or
single amino acid variants (SAAVs). Besides unique peptides of missing
proteins, identified variant peptides (SAAV-containing peptides) could
also alternatively map to peptides of other proteins due to the aforementioned
issues. Therefore, we conducted a thorough comparative analysis on
data sets in PeptideAtlas Tiered Human Integrated Search Proteome
(THISP, 2017-03 release), including neXtProt (2017-01 release), to
systematically investigate the possibility of unique peptides in missing
proteins (PE2–4), unique peptides in dubious proteins, and
variant peptides affected by isobaric substitutions, causing doubtful
identification results. In this study, we considered 11 isobaric substitutions.
From our analysis, we found <5% of the unique peptides of missing
proteins and >6% of variant peptides became shared with peptides
of
PE1 proteins after isobaric substitutions
Decoding the Effect of Isobaric Substitutions on Identifying Missing Proteins and Variant Peptides in Human Proteome
To
confirm the existence of missing proteins, we need to identify
at least two unique peptides with length of 9–40 amino acids
of a missing protein in bottom-up mass-spectrometry-based proteomic
experiments. However, an identified unique peptide of the missing
protein, even identified with high level of confidence, could possibly
coincide with a peptide of a commonly observed protein due to isobaric
substitutions, mass modifications, alternative splice isoforms, or
single amino acid variants (SAAVs). Besides unique peptides of missing
proteins, identified variant peptides (SAAV-containing peptides) could
also alternatively map to peptides of other proteins due to the aforementioned
issues. Therefore, we conducted a thorough comparative analysis on
data sets in PeptideAtlas Tiered Human Integrated Search Proteome
(THISP, 2017-03 release), including neXtProt (2017-01 release), to
systematically investigate the possibility of unique peptides in missing
proteins (PE2–4), unique peptides in dubious proteins, and
variant peptides affected by isobaric substitutions, causing doubtful
identification results. In this study, we considered 11 isobaric substitutions.
From our analysis, we found <5% of the unique peptides of missing
proteins and >6% of variant peptides became shared with peptides
of
PE1 proteins after isobaric substitutions
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Expression of miR-124 inhibits growth of medulloblastoma cells.
Medulloblastoma is the most common malignant brain tumor in children, and a substantial number of patients die as a result of tumor progression. Overexpression of CDK6 is present in approximately one-third of medulloblastomas and is an independent poor prognostic marker for this disease. MicroRNA (miR)-124 inhibits expression of CDK6 and prevents proliferation of glioblastoma and medulloblastoma cells in vitro. We examined the effects of miR-124 overexpression on medulloblastoma cells both in vitro and in vivo and compared cell lines that have low and high CDK6 expression. MiR-124 overexpression inhibits the proliferation of medulloblastoma cells, and this effect is mediated mostly through the action of miR-124 upon CDK6. We further show that induced expression of miR-124 potently inhibits growth of medulloblastoma xenograft tumors in rodents. Further testing of miR-124 will help define the ultimate therapeutic potential of preclinical models of medulloblastoma in conjunction with various delivery strategies for treatment
DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples
Protein–protein
interactions (PPIs) are fundamental to understanding
biological systems as protein complexes are the active molecular modules
critical for carrying out cellular functions. Dysfunctional PPIs have
been associated with various diseases including cancer. Systems-wide
PPI analysis not only sheds light on pathological mechanisms, but
also represents a paradigm in identifying potential therapeutic targets.
In recent years, cross-linking mass spectrometry (XL-MS) has emerged
as a powerful tool for defining endogenous PPIs of cellular networks.
While proteome-wide studies have been performed in cell lysates, intact
cells and tissues, applications of XL-MS in clinical samples have
not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from
two breast cancer patient-derived xenograft (PDX) models. As a result,
we have generated a PDX interaction network comprising 2,557 human
proteins and identified interactions unique to breast cancer subtypes.
Interestingly, most of the observed differences in PPIs correlated
well with protein abundance changes determined by TMT-based proteome
quantitation. Collectively, this work has demonstrated the feasibility
of XL-MS analysis in clinical samples, and established an analytical
workflow for tissue cross-linking that can be generalized for mapping
PPIs from patient samples in the future to dissect disease-relevant
cellular networks
DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples
Protein–protein
interactions (PPIs) are fundamental to understanding
biological systems as protein complexes are the active molecular modules
critical for carrying out cellular functions. Dysfunctional PPIs have
been associated with various diseases including cancer. Systems-wide
PPI analysis not only sheds light on pathological mechanisms, but
also represents a paradigm in identifying potential therapeutic targets.
In recent years, cross-linking mass spectrometry (XL-MS) has emerged
as a powerful tool for defining endogenous PPIs of cellular networks.
While proteome-wide studies have been performed in cell lysates, intact
cells and tissues, applications of XL-MS in clinical samples have
not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from
two breast cancer patient-derived xenograft (PDX) models. As a result,
we have generated a PDX interaction network comprising 2,557 human
proteins and identified interactions unique to breast cancer subtypes.
Interestingly, most of the observed differences in PPIs correlated
well with protein abundance changes determined by TMT-based proteome
quantitation. Collectively, this work has demonstrated the feasibility
of XL-MS analysis in clinical samples, and established an analytical
workflow for tissue cross-linking that can be generalized for mapping
PPIs from patient samples in the future to dissect disease-relevant
cellular networks
DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples
Protein–protein
interactions (PPIs) are fundamental to understanding
biological systems as protein complexes are the active molecular modules
critical for carrying out cellular functions. Dysfunctional PPIs have
been associated with various diseases including cancer. Systems-wide
PPI analysis not only sheds light on pathological mechanisms, but
also represents a paradigm in identifying potential therapeutic targets.
In recent years, cross-linking mass spectrometry (XL-MS) has emerged
as a powerful tool for defining endogenous PPIs of cellular networks.
While proteome-wide studies have been performed in cell lysates, intact
cells and tissues, applications of XL-MS in clinical samples have
not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from
two breast cancer patient-derived xenograft (PDX) models. As a result,
we have generated a PDX interaction network comprising 2,557 human
proteins and identified interactions unique to breast cancer subtypes.
Interestingly, most of the observed differences in PPIs correlated
well with protein abundance changes determined by TMT-based proteome
quantitation. Collectively, this work has demonstrated the feasibility
of XL-MS analysis in clinical samples, and established an analytical
workflow for tissue cross-linking that can be generalized for mapping
PPIs from patient samples in the future to dissect disease-relevant
cellular networks
DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples
Protein–protein
interactions (PPIs) are fundamental to understanding
biological systems as protein complexes are the active molecular modules
critical for carrying out cellular functions. Dysfunctional PPIs have
been associated with various diseases including cancer. Systems-wide
PPI analysis not only sheds light on pathological mechanisms, but
also represents a paradigm in identifying potential therapeutic targets.
In recent years, cross-linking mass spectrometry (XL-MS) has emerged
as a powerful tool for defining endogenous PPIs of cellular networks.
While proteome-wide studies have been performed in cell lysates, intact
cells and tissues, applications of XL-MS in clinical samples have
not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from
two breast cancer patient-derived xenograft (PDX) models. As a result,
we have generated a PDX interaction network comprising 2,557 human
proteins and identified interactions unique to breast cancer subtypes.
Interestingly, most of the observed differences in PPIs correlated
well with protein abundance changes determined by TMT-based proteome
quantitation. Collectively, this work has demonstrated the feasibility
of XL-MS analysis in clinical samples, and established an analytical
workflow for tissue cross-linking that can be generalized for mapping
PPIs from patient samples in the future to dissect disease-relevant
cellular networks
DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples
Protein–protein
interactions (PPIs) are fundamental to understanding
biological systems as protein complexes are the active molecular modules
critical for carrying out cellular functions. Dysfunctional PPIs have
been associated with various diseases including cancer. Systems-wide
PPI analysis not only sheds light on pathological mechanisms, but
also represents a paradigm in identifying potential therapeutic targets.
In recent years, cross-linking mass spectrometry (XL-MS) has emerged
as a powerful tool for defining endogenous PPIs of cellular networks.
While proteome-wide studies have been performed in cell lysates, intact
cells and tissues, applications of XL-MS in clinical samples have
not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from
two breast cancer patient-derived xenograft (PDX) models. As a result,
we have generated a PDX interaction network comprising 2,557 human
proteins and identified interactions unique to breast cancer subtypes.
Interestingly, most of the observed differences in PPIs correlated
well with protein abundance changes determined by TMT-based proteome
quantitation. Collectively, this work has demonstrated the feasibility
of XL-MS analysis in clinical samples, and established an analytical
workflow for tissue cross-linking that can be generalized for mapping
PPIs from patient samples in the future to dissect disease-relevant
cellular networks
DSBSO-Based XL-MS Analysis of Breast Cancer PDX Tissues to Delineate Protein Interaction Network in Clinical Samples
Protein–protein
interactions (PPIs) are fundamental to understanding
biological systems as protein complexes are the active molecular modules
critical for carrying out cellular functions. Dysfunctional PPIs have
been associated with various diseases including cancer. Systems-wide
PPI analysis not only sheds light on pathological mechanisms, but
also represents a paradigm in identifying potential therapeutic targets.
In recent years, cross-linking mass spectrometry (XL-MS) has emerged
as a powerful tool for defining endogenous PPIs of cellular networks.
While proteome-wide studies have been performed in cell lysates, intact
cells and tissues, applications of XL-MS in clinical samples have
not been reported. In this study, we adopted a DSBSO-based in vivo XL-MS platform to map interaction landscapes from
two breast cancer patient-derived xenograft (PDX) models. As a result,
we have generated a PDX interaction network comprising 2,557 human
proteins and identified interactions unique to breast cancer subtypes.
Interestingly, most of the observed differences in PPIs correlated
well with protein abundance changes determined by TMT-based proteome
quantitation. Collectively, this work has demonstrated the feasibility
of XL-MS analysis in clinical samples, and established an analytical
workflow for tissue cross-linking that can be generalized for mapping
PPIs from patient samples in the future to dissect disease-relevant
cellular networks