RRP1B is a Metastasis Modifier that Regulates the Transcriptome through mRNA Splicing
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE38669 | GEO | 2014/06/08
SECONDARY ACCESSION(S): PRJNA168458
REPOSITORIES: GEO
Similar Datasets
Project description:RRP1B is a Metastasis Modifier that Regulates the Transcriptome through mRNA Splicing To assess the role of RRP1B in alternative mRNA splicing, we knocked down the expression of Rrp1b in the highly metastatic mouse mammary tumor cell line Mvt-1 using shRNA. Two control and two knockdown stable cell lines were selected for RNA-sequencing.
2014-06-08 | E-GEOD-38669 | biostudies-arrayexpress
Project description:Smarcd1 is a “Goldilocks” metastasis modifier gene
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Project description:Breast cancer is the most highly diagnosed cancer worldwide, making up around 12% of all diagnosed cancers in 2020. Mortality caused by breast cancer is largely due to metastasis to distant essential organs, and a lack of metastasis-targeted therapies perpetuates incredibly poor outcomes for late-stage patients. Here we have identified a new class of “Goldilocks” genes for metastasis-targeted therapeutic development, through our focus on meiotic genetics and inherited transcriptional network regulation. Building on previous work identifying the CCR4-NOT RNA deadenylase complex in metastasis, we further demonstrate that RNA binding proteins NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using cell lines, 3D culture, mouse models, and clinical data, we have identified Smarcd1 mRNA, a key target of all three factors, for which high and low expression is associated with positive clinical outcome, but medium expression significantly reduces probability of survival. Applying the theory of “essential genes” from evolution, we have identified an additional 50 genes that span several cellular processes and must be maintained within a discrete window of expression for metastasis to occur. In the case of Smarcd1, small perturbations in expression level significantly reduced metastasis in laboratory mouse models and altered splicing programs of particular relevance to the ER+HER2 enriched patient subtype. Identification of subtype-specific “Golidlocks” metastasis modifier genes creates a new class of genes and catalogue of potential novel targets that when therapeutically “nudged” in either direction may significantly improve late-stage patient outcomes.
2024-10-03 | GSE260680 | GEO
Project description:Smarcd1 is a “Goldilocks” metastasis modifier gene [rnaseq_spheroids]
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Project description:Smarcd1 is a “Goldilocks” metastasis modifier gene [ATAC_on_plastic]
| PRJNA1082360 | ENA
Project description:Breast cancer is the most highly diagnosed cancer worldwide, making up around 12% of all diagnosed cancers in 2020. Mortality caused by breast cancer is largely due to metastasis to distant essential organs, and a lack of metastasis-targeted therapies perpetuates incredibly poor outcomes for late-stage patients. Here we have identified a new class of “Goldilocks” genes for metastasis-targeted therapeutic development, through our focus on meiotic genetics and inherited transcriptional network regulation. Building on previous work identifying the CCR4-NOT RNA deadenylase complex in metastasis, we further demonstrate that RNA binding proteins NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using cell lines, 3D culture, mouse models, and clinical data, we have identified Smarcd1 mRNA, a key target of all three factors, for which high and low expression is associated with positive clinical outcome, but medium expression significantly reduces probability of survival. Applying the theory of “essential genes” from evolution, we have identified an additional 50 genes that span several cellular processes and must be maintained within a discrete window of expression for metastasis to occur. In the case of Smarcd1, small perturbations in expression level significantly reduced metastasis in laboratory mouse models and altered splicing programs of particular relevance to the ER+HER2 enriched patient subtype. Identification of subtype-specific “Golidlocks” metastasis modifier genes creates a new class of genes and catalogue of potential novel targets that when therapeutically “nudged” in either direction may significantly improve late-stage patient outcomes.
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Project description:Breast cancer is the most highly diagnosed cancer worldwide, making up around 12% of all diagnosed cancers in 2020. Mortality caused by breast cancer is largely due to metastasis to distant essential organs, and a lack of metastasis-targeted therapies perpetuates incredibly poor outcomes for late-stage patients. Here we have identified a new class of “Goldilocks” genes for metastasis-targeted therapeutic development, through our focus on meiotic genetics and inherited transcriptional network regulation. Building on previous work identifying the CCR4-NOT RNA deadenylase complex in metastasis, we further demonstrate that RNA binding proteins NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using cell lines, 3D culture, mouse models, and clinical data, we have identified Smarcd1 mRNA, a key target of all three factors, for which high and low expression is associated with positive clinical outcome, but medium expression significantly reduces probability of survival. Applying the theory of “essential genes” from evolution, we have identified an additional 50 genes that span several cellular processes and must be maintained within a discrete window of expression for metastasis to occur. In the case of Smarcd1, small perturbations in expression level significantly reduced metastasis in laboratory mouse models and altered splicing programs of particular relevance to the ER+HER2 enriched patient subtype. Identification of subtype-specific “Golidlocks” metastasis modifier genes creates a new class of genes and catalogue of potential novel targets that when therapeutically “nudged” in either direction may significantly improve late-stage patient outcomes.
2024-10-03 | GSE260622 | GEO
Project description:The processing of RNAs by chromatin-associated proteins (CAPs) is highlighted by the latest findings. However, whether and how CAP-RNA interactions regulate cancer biology remain underdefined. Using modified fCLIP-seq technology, we show that, cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, binds bulk transcripts, preferentially at splicing-responsible motifs, influencing the abundance and alternative splicing (AS) of target transcripts, preferentially those encoding mitosis regulators. MTA1 orchestrates the fluctuant pre-mRNA AS kinetics of mitosis regulators, such as ATRX and MYBL2, during mitosis. MTA1 overexpression causes a defective mitotic arrest, leading to aberrant chromosome segregation, and CIN occurrence in cancer cells and clinical tumors, which eventually contributes to tumorigenesis. Hence, we present MTA1 as a pivotal RNA-binding CAP linked to mitosis control in tumorigenesis.
2020-07-17 | GSE123956 | GEO
Project description:The processing of RNAs by chromatin-associated proteins (CAPs) is highlighted by the latest findings. However, whether and how CAP-RNA interactions regulate cancer biology remain underdefined. Using modified fCLIP-seq technology, we show that, cancer metastasis-associated antigen 1 (MTA1), a well-known oncogenic chromatin modifier, binds bulk transcripts, preferentially at splicing-responsible motifs, influencing the abundance and alternative splicing (AS) of target transcripts, preferentially those encoding mitosis regulators. MTA1 orchestrates the fluctuant pre-mRNA AS kinetics of mitosis regulators, such as ATRX and MYBL2, during mitosis. MTA1 overexpression causes a defective mitotic arrest, leading to aberrant chromosome segregation, and CIN occurrence in cancer cells and clinical tumors, which eventually contributes to tumorigenesis. Hence, we present MTA1 as a pivotal RNA-binding CAP linked to mitosis control in tumorigenesis.
2020-07-17 | GSE123955 | GEO
Project description:Breast cancer is the most highly diagnosed cancer worldwide, making up around 12% of all diagnosed cancers in 2020. Mortality caused by breast cancer is largely due to metastasis to distant essential organs, and a lack of metastasis-targeted therapies perpetuates incredibly poor outcomes for late-stage patients. Here we have identified a new class of “Goldilocks” genes for metastasis-targeted therapeutic development, through our focus on meiotic genetics and inherited transcriptional network regulation. Building on previous work identifying the CCR4-NOT RNA deadenylase complex in metastasis, we further demonstrate that RNA binding proteins NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using cell lines, 3D culture, mouse models, and clinical data, we have identified Smarcd1 mRNA, a key target of all three factors, for which high and low expression is associated with positive clinical outcome, but medium expression significantly reduces probability of survival. Applying the theory of “essential genes” from evolution, we have identified an additional 50 genes that span several cellular processes and must be maintained within a discrete window of expression for metastasis to occur. In the case of Smarcd1, small perturbations in expression level significantly reduced metastasis in laboratory mouse models and altered splicing programs of particular relevance to the ER+HER2 enriched patient subtype. Identification of subtype-specific “Golidlocks” metastasis modifier genes creates a new class of genes and catalogue of potential novel targets that when therapeutically “nudged” in either direction may significantly improve late-stage patient outcomes.
2024-10-03 | GSE260672 | GEO