Smarcd1 is a “Goldilocks” metastasis modifier gene [RNA-seq_on_plastic]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1082719 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28196067_1.fastq.gz | Fastqsanger.gz | |||
| SRR28196067_2.fastq.gz | Fastqsanger.gz | |||
| SRR28196068_1.fastq.gz | Fastqsanger.gz | |||
| SRR28196068_2.fastq.gz | Fastqsanger.gz | |||
| SRR28196069_1.fastq.gz | Fastqsanger.gz |
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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 | GSE260672 | 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 | GSE260680 | 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 | GSE260622 | 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 | GSE260621 | GEO
Project description:Breast cancer is the most frequently diagnosed cancer worldwide, constituting around 15% of all diagnosed cancers in 2023. The predominant cause of breast cancer-related mortality is metastasis to distant essential organs, and a lack of metastasis-targeted therapies perpetuates dismal outcomes for late-stage patients. However, through our use of meiotic genetics to study inherited transcriptional network regulation, we have identified a new class of "Goldilocks" genes that are promising candidates for the development of metastasis-targeted therapeutics. Building upon previous work that implicated the CCR4-NOT RNA deadenylase complex in metastasis, we now demonstrate that the RNA-binding proteins (RNA-BPs) NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using cell lines, 3D culture, mouse models, and clinical data, we pinpoint Smarcd1 mRNA as a key target of all three RNA-BPs. Strikingly, both high and low expression of Smarcd1 is associated with positive clinical outcomes, while intermediate expression significantly reduces the probability of survival. Applying the theory of "essential genes" from evolution, we identify 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 its expression level significantly reduce metastasis in laboratory mouse models and alter splicing programs relevant to the ER+/HER2-enriched breast cancer subtype. The identification of subtype-specific "Goldilocks" metastasis modifier genes introduces a new class of genes and potential catalogue of novel targets that, when therapeutically "nudged" in either direction, may significantly improve late-stage patient outcomes.
| S-EPMC10896335 | biostudies-literature
Project description:Breast cancer is the most frequently diagnosed cancer worldwide, constituting 15% of cases in 2023. The predominant cause of breast cancer-related mortality is metastasis, and a lack of metastasis-targeted therapies perpetuates dismal outcomes for late-stage patients. By using meiotic genetics to study inherited transcriptional network regulation, we have identified, to the best of our knowledge, a new class of "essential expression-restricted" genes as potential candidates for metastasis-targeted therapeutics. Building upon previous work implicating the CCR4-NOT RNA deadenylase complex in metastasis, we demonstrate that RNA-binding proteins NANOS1, PUM2, and CPSF4 also regulate metastatic potential. Using various models and clinical data, we pinpoint Smarcd1 mRNA as a target of all three RNA-BPs. Strikingly, both high and low expression of Smarcd1 correlate with positive clinical outcomes, while intermediate expression significantly reduces the probability of survival. Applying the theory of "essential genes" from evolution, we identify 50 additional genes that require precise expression levels for metastasis to occur. Specifically, small perturbations in Smarcd1 expression significantly reduce metastasis in mouse models and alter splicing programs relevant to the ER+/HER2-enriched breast cancer. Identification subtype-specific essential expression-restricted metastasis modifiers introduces a novel class of genes that, when therapeutically "nudged" in either direction, may significantly improve late-stage breast cancer patients.
| S-EPMC11467182 | biostudies-literature
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