Cancer-induced FOXP1 disrupts and reprograms skeletal muscle circadian transcription in cachexia [ChIP-seq]
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ABSTRACT:
PROVIDER: PRJNA1142901 | ENA |
REPOSITORIES: ENA
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Project description:Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mortality. We previously found that Forkhead box P1 (FoxP1) upregulation in skeletal muscle causes muscle wasting and is required for muscle wasting in response to cancer. However, transcriptional networks targeted by FoxP1 in skeletal muscles undergoing cancer-induced wasting remain largely unknown. Here, we identify FoxP1 as a key disruptor of the skeletal muscle clock in response to cancer, that reprograms circadian patterns of gene expression at cachexia onset. Specifically, we show that cancer-induced FoxP1 rewires the skeletal muscle circadian transcriptome towards pathways associated with muscle wasting and disrupts the temporal patterning of pathways governing glucose, lipid, and oxidative metabolism. These findings thus implicate cancer/disease-specific functions of FOXP1 in the disruption and reprograming of the skeletal muscle circadian transcriptome which may contribute to muscle wasting and the development of cachexia.
2025-05-11 | GSE273878 | GEO
Project description:Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mortality. We previously found that Forkhead box P1 (FoxP1) upregulation in skeletal muscle causes muscle wasting and is required for muscle wasting in response to cancer. However, transcriptional networks targeted by FoxP1 in skeletal muscles undergoing cancer-induced wasting remain largely unknown. Here, we identify FoxP1 as a key disruptor of the skeletal muscle clock in response to cancer, that reprograms circadian patterns of gene expression at cachexia onset. Specifically, we show that cancer-induced FoxP1 rewires the skeletal muscle circadian transcriptome towards pathways associated with muscle wasting and disrupts the temporal patterning of pathways governing glucose, lipid, and oxidative metabolism. These findings thus implicate cancer/disease-specific functions of FOXP1 in the disruption and reprograming of the skeletal muscle circadian transcriptome which may contribute to muscle wasting and the development of cachexia.
2025-05-11 | GSE273712 | GEO
Project description:Cancer cachexia is a debilitating metabolic disorder characterized by involuntary loss of body and muscle mass, leading to increased morbidity and mortality. We previously found that Forkhead box P1 (FoxP1) upregulation in skeletal muscle causes muscle wasting and is required for muscle wasting in response to cancer. However, transcriptional networks targeted by FoxP1 in skeletal muscles undergoing cancer-induced wasting remain largely unknown. Here, we identify FoxP1 as a key disruptor of the skeletal muscle clock in response to cancer, that reprograms circadian patterns of gene expression at cachexia onset. Specifically, we show that cancer-induced FoxP1 rewires the skeletal muscle circadian transcriptome towards pathways associated with muscle wasting and disrupts the temporal patterning of pathways governing glucose, lipid, and oxidative metabolism. These findings thus implicate cancer/disease-specific functions of FOXP1 in the disruption and reprograming of the skeletal muscle circadian transcriptome which may contribute to muscle wasting and the development of cachexia.
2025-05-11 | GSE273879 | GEO
Project description:Cancer-induced FOXP1 disrupts and reprograms skeletal muscle circadian transcription in cachexia [circadian RNA-seq]
| PRJNA1143531 | ENA
Project description:Cancer-induced FOXP1 disrupts and reprograms skeletal muscle circadian transcription in cachexia [skeletal muscle overexpression of FoxP1 RNA-seq]
| PRJNA1143530 | ENA
Project description:Skeletal muscle wasting is a devastating consequence of cancer that affects up to 80% of cancer patients and associates with reduced survival. Herein we identified the transcriptional repressor protein, Forkhead box P1 (FoxP1), as a downstream target gene of FoxO1 whose skeletal muscle expression is elevated in multiple models of cancer cachexia and in patients with cancer who exhibit cachexia. Through generation of inducible skeletal muscle-specific FoxP1 over-expressing (FoxP1iSkmTg/Tg) mice, we demonstrate that FoxP1 upregulation is sufficient to induce features of cachexia, including body and skeletal muscle wasting characterized by reduced muscle fiber cross-sectional area of type IIX/B muscle fibers. Muscles from FoxP1iSkmTg/Tg mice also showed significant muscle damage and myopathy characterized by the accumulation of p62 and cellular material-filled vesicles, the presence of centrally nucleated myofibers, and were significantly weaker than controls. In the context of cancer cachexia, blocking FoxP1 upregulation prevented the cancer-induced repression of target genes critical to muscle structural integrity and repair, including Myocyte enhancer factor 2c (Mef2c), improved muscle ultrastructure and significantly attenuated muscle fiber atrophy. We further show that the muscle wasting phenotype induced by FoxP1 required the activity of histone deacetylase (HDAC) proteins, which are well-established to cooperate with FoxP1 to mediate gene repression, and which were necessary for FoxP1-dependent repression of Mef2c. In summary, we identify FoxP1 as a negative transcriptional regulator of skeletal muscle mass and function, whose up-regulation mediates cancer-induced muscle wasting. We used microarrays to investigate the genome-wide transcriptional networks regulated by the FoxO1 and FoxP1 transcription factors in skeletal muscle of tumor-bearing mice.
2021-04-28 | GSE153068 | GEO
Project description:Empirical evidence from both animals and humans suggest that PM2.5 (particulate matter < 2.5μm) exposure accelerates a variety of non-communicable diseases (NCDs) including Type 2 diabetes. We investigated whether chronic exposure to ambient air pollution (PM2.5), disrupts circadian rhythm to facilitate metabolic insulin resistance and compared the impact of inhaled ambient PM2.5 alone or in combination with continuous light exposure (LL). Exposure to PM2.5 induced peripheral IR, disrupted circadian steroid release, reduced peak oxygen consumption and altered brown adipose 18Ffluorodeoxyglucose uptake on PET imaging. These findings were identical to that seen with LL with no additive interaction between PM2.5 and LL. Transcriptome profiles in the liver revealed a number of differentially expressed circadian genes Bmal1 (Arntl/Npas2), Period (Per) and Cryptochrome (Cry) in response to PM2.5. Alteration in chromatin accessibility in circadian targets was observed with PM2.5 by Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) while chromatin immunoprecipitation (ChIP) analysis, showed a marked difference in promoter occupancy by p300. Our data suggest a previously unrecognized role of particulate air pollution in promoting circadian disruption and metabolic dysfunction through epigenetic regulation of multiple circadian targets
2020-12-01 | GSE145566 | GEO
Project description:Identification of peptides matching to LCK in FOXP1 immunoprecipitates from HONE1 cells by mass spectrometry
2022-04-04 | PXD031014 | Pride
Project description:The transcription factor FOXP1 is implicated in the pathogenesis of B-cell lymphomas through immunoglobulin heavy chain (IGH) locus-related chromosomal translocations leading to dysregulated expression of FOXP1. Translocations of FOXP1 with non-IG gene sequences have been also reported, but the molecular consequences of such aberrations remain undetermined. Here, using molecular cytogenetics and molecular biology studies, we comprehensively analyzed four lymphoma cases with non-IG rearrangements of FOXP1 and compared these with cases harboring t(3;14)(p13;q32)/IGH-FOXP1 and FOXP1-expressing lymphomas without underlying t(3p13/FOXP1). We found that non-IG rearrangements are usually acquired during evolution of lymphoma and constantly target the coding region of FOXP1, promiscuously fusing with coding and non-coding gene sequences at various reciprocal breakpoints (2q36, 10q24 and 3q11). Intriguingly, these rearrangements do not generate functional chimeric genes but commonly disrupt the full-length FOXP1 transcript leading to an aberrant expression of N-truncated FOXP1 isoforms, as shown by QRT-PCR and Western blot analysis. In contrast, cases with t(3;14)(p13;q32)/IGH-FOXP1 overexpress the full-length FOXP1. Collectively, our findings point to a dual mechanism through which FOXP1 is implicated in B-cell lymphomagenesis. The primary t(3;14)(p13;q32)/IGH-FOXP1 produces the full-length protein with potent oncogenic activity, whereas the secondary non-IG 17 rearrangements of FOXP1 generate N-truncated FOXP1 isoforms, likely driving progression of disease. Using molecular cytogenetics and molecular biology studies (including RNA-seq), we comprehensively analyzed four lymphoma cases with non-IG rearrangements of FOXP1 and compared these with cases harboring t(3;14)(p13;q32)/IGH-FOXP1 and FOXP1-expressing lymphomas without underlying t(3p13/FOXP1).
2013-09-04 | E-GEOD-50514 | biostudies-arrayexpress