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The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway [ChIP-Seq]

ABSTRACT: The aim of this study is to identify the SPIN1 target genes in liposarcoma cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE57499 | GEO | 2017/02/09

SECONDARY ACCESSION(S): PRJNA246554

REPOSITORIES: GEO

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The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway [RNA-Seq]

Project description:The aim of this study is to identify the SPIN1 target genes in liposarcoma cells

2017-02-09 | GSE57501 | GEO

The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway

Project description:The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway

| PRJNA246553 | ENA

The histone code reader SPIN1 controls RET signaling in liposarcoma.

Project description:The histone code reader Spindlin1 (SPIN1) has been implicated in tumorigenesis and tumor growth, but the underlying molecular mechanisms remain poorly understood. Here, we show that reducing SPIN1 levels strongly impairs proliferation and increases apoptosis of liposarcoma cells in vitro and in xenograft mouse models. Combining signaling pathway, genome-wide chromatin binding, and transcriptome analyses, we found that SPIN1 directly enhances expression of GDNF, an activator of the RET signaling pathway, in cooperation with the transcription factor MAZ. Accordingly, knockdown of SPIN1 or MAZ results in reduced levels of GDNF and activated RET explaining diminished liposarcoma cell proliferation and survival. In line with these observations, levels of SPIN1, GDNF, activated RET, and MAZ are increased in human liposarcoma compared to normal adipose tissue or lipoma. Importantly, a mutation of SPIN1 within the reader domain interfering with chromatin binding reduces liposarcoma cell proliferation and survival. Together, our data describe a molecular mechanism for SPIN1 function in liposarcoma and suggest that targeting SPIN1 chromatin association with small molecule inhibitors may represent a novel therapeutic strategy.

| S-EPMC4467114 | biostudies-literature

The epigenetic reader protein SPIN1 controls proliferation and survival of liposarcoma by modulating the RET signaling pathway

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-02-09 | GSE57502 | GEO

The histone code reader Spin1 controls skeletal muscle development

Project description:We report developmental defects in Spin1(Myf5-Cre) mice, in which Spin1 is ablated in skeletal muscle.

2017-12-08 | GSE92539 | GEO

The histone code reader Spin1 controls skeletal muscle development.

Project description:While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1M5 mice with ablation of Spin1 in myoblast precursors using the Myf5-Cre deleter strain. Most Spin1M5 mice die shortly after birth displaying severe sarcomere disorganization and necrosis. Surviving Spin1M5 mice are growth-retarded and exhibit the most prominent defects in soleus, tibialis anterior, and diaphragm muscle. Transcriptome analyses of limb muscle at embryonic day (E) 15.5, E16.5, and at three weeks of age provided evidence for aberrant fetal myogenesis and identified deregulated skeletal muscle (SkM) functional networks. Determination of genome-wide chromatin occupancy in primary myoblast revealed direct Spin1 target genes and suggested that deregulated basic helix-loop-helix transcription factor networks account for developmental defects in Spin1M5 fetuses. Furthermore, correlating histological and transcriptome analyses, we show that aberrant expression of titin-associated proteins, abnormal glycogen metabolism, and neuromuscular junction defects contribute to SkM pathology in Spin1M5 mice. Together, we describe the first example of a histone code reader controlling SkM development in mice, which hints at Spin1 as a potential player in human SkM disease.

| S-EPMC5775400 | biostudies-literature

The intrinsically disordered region of SPIN1 regulates its function by phase separation [ChIP-seq]

Project description:As a transcriptional coactivator, SPIN1 has been reported to bind to chromatin.To assess the effect of IDR on chromatin binding, we investigated genome-wide chromatin association of SPIN1-WT or SPIN1-△IDR stably overexpressed cell lines by chromatin immunoprecipitation followed by high-throughput sequencing.

2024-12-19 | GSE215398 | GEO

SPIN1 accelerates tumorigenesis and confers radioresistance of non-small cell lung cancer via orchestrating the FOXO3a/FOXM1 axis

Project description:Radioresistance is a predominant obstacle of effective treatments in non-small cell lung cancer (NSCLC), while the underlying mechanism remains incompletely elucidated. Spindlin 1(SPIN1) has been reported to participate in tumor initiation and progression, while its role in NSCLC tumorigenesis and radioresistance remains largely unknown. In this study, bioinformatics analysis, immunohistochemistry (IHC) and western blotting assays were performed to test SPIN1 expression in NSCLC samples and cell lines. The carcinogenic role of SPIN1 was evaluated by cell growth and proliferation, EdU staining, transwell and colony formation assays. Besides, the radiosensitivity of NSCLC cells was determined by clonogenic cell survival, neutral comet and γ-H2AX and Rad51 foci formation assays. Xenograft tumor model was constructed to access the effects of SPIN1 on tumorigenesis and radiosensitivity. Furthermore, RNA sequencing, quantitative real-time PCR, CHX and ubiquitination assays were applied to elucidate the correlation between SPIN1 and FOXO3a-FOXM1 axis. Therefore, our results suggest that the SPIN1-MDM2-FOXO3a/FOXM1 signaling axis is essential for NSCLC progression and radioresistance, and it could serve as therapeutic targets in irradiation-resistance NSCLC.

2024-11-20 | GSE276500 | GEO

Gene expression signatures in SPIN1 siRNA- and negative control-transfected breast cancer cell line MCF-7/ADM

Project description:To screen potential target genes of SPIN1 in breast cancer, human gene expression microarray was performed to identify differentially expressed mRNAs in SPIN1 siRNA or negative control transfected MCF-7/ADM cells. After transfection with SPIN1 siRNA, 4409 genes were differentially expressed by >2-fold in MCF-7/ADM cells compared with negative control-transfected cells, of which 2413 were significantly downregulated and the other 1996 were upregulated. Differentially expressed genes were submitted to GO and KEGG pathway analysis.

2017-08-01 | GSE71141 | GEO

Whole genome microarray analysis in myxoid liposarcoma

Project description:In order to identify new key molecules in the pathogenesis of myxoid liposarcoma, we performed comparative gene expression profiling in myxoid liposarcoma and fat tissue samples.

2014-10-28 | GSE62747 | GEO

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