SND1-SMARCA5 interaction strengthened by PIM promoted the proliferation, metastasis and chemoresistance of ESCC
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1183737 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31296466_1.fastq.gz | Fastqsanger.gz | |||
| SRR31296466_2.fastq.gz | Fastqsanger.gz | |||
| SRR31296467_1.fastq.gz | Fastqsanger.gz | |||
| SRR31296467_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:Chromatin remodeling plays a pivotal role in the progression of esophageal squamous cell carcinoma (ESCC), yet the precise mechanisms remain poorly understood. Here, we elucidate the critical function of staphylococcal nuclease and tudor domain-containing 1 (SND1) in modulating chromatin dynamics, thereby driving ESCC progression in both in vitro and in vivo models. Our data revealed that SND1 was markedly overexpressed in ESCC cell lines. Silencing SND1 disrupted histone modifications, attenuated RNA polymerase II activity, and precipitated increased chromosomal aberrations and DNA damage, particularly following camptothecin treatment. These molecular perturbations culminated in diminished cellular proliferation, metastasis and chemoresistance. We further identified that the regulatory effects of SND1 on chromatin are mediated through its interaction with SMARCA5, a process potentiated by PIM1-catalyzed phosphorylation of SND1 at serine 426. This SND1-SMARCA5 interaction is essential for the transcriptional activation of CUX1, a key oncogene implicated in ESCC progression. Notably, disruption of SND1S426 phosphorylation impaired the SND1-SMARCA5 interaction, leading to significant inhibition of ESCC tumor growth and metastatic potential in vivo. Our findings unveil a novel mechanistic axis involving SND1 and SMARCA5 in chromatin remodeling and oncogenesis, offering promising therapeutic targets for ESCC intervention.
2025-02-08 | GSE281371 | GEO
Project description:We hypothesize that the ISWI ATPase Smarca5 plays a role in hematopoietic stem cell development via its interaction partners, and to study the role, we used a mouse model with transgenic expression of SMARCA5 coupled with mass spectrometry analysis. The study uses transgenic SMARCA5 mouse model with conditional hypomorphic allele (lower expression on protein level compared to controls) incorporated into Rosa26 locus, transgenic allele uses endogenous Rosa26 promoter. The transgenic human SMARCA5 protein has a FLAG tag at its C-terminus, which allows specific immunoprecipitation and also differentiation from the endogenous protein (human and mouse SMARCA5 are almost identical at the protein level). To ensure the highest possible expression of the transgenic allele, we used a model that also had one endogenous Smarca5 allele deleted. Various organs (thymus, spleen, brain, kidney, liver, testes, muscle, fetal liver) were isolated from transgenic mice, lysed and then immunoprecipitated using anti-FLAG antibody. The immunoprecipitates were then analyzed using mass spectrometry to determine SMARCA5 interactomes in various tissues. Transgenic human SMARCA5 was confirmed to form all the expected complexes and capable of replacing the functions of the mouse protein. For details, see the publication of Turkova et al. 2024 in Communications Biology.
2024-06-22 | PXD049034 | Pride
Project description:PIM kinases have important pro-tumorigenic roles and mediate several oncogenic traits, including cell proliferation, survival, and chemotherapeutic resistance. As a result, multiple PIM inhibitors have been pursued as investigational new drugs in cancer; however, response to PIM inhibitors in solid tumors has fallen short of expectations. We found that inhibition of PIM kinase activity stabilizes protein levels of all three PIM isoforms (PIM1/2/3), and this can promote resistance to PIM inhibitors and chemotherapy. To overcome this effect, we designed PIM proteolysis targeting chimeras (PROTACs) to target PIM for degradation. PIM PROTACs effectively downmodulated PIM levels through the ubiquitin-proteasome pathway. Importantly, degradation of PIM kinases was more potent than inhibition of catalytic activity in inducing apoptosis in prostate cancer cell line models. In conclusion, we provide evidence of the advantages of degrading PIM kinases versus inhibiting their catalytic activity to target the oncogenic functions of PIM kinases.
2023-12-04 | GSE237256 | GEO
Project description:Staphylococcal nuclease Tudor domain containing 1 (SND1) protein is an oncogene that “reads” methylarginine marks through its Tudor domain. Specifically, it recognizes methylation marks deposited by protein arginine methyltransferase 5 (PRMT5), which is also known to promote tumorigenesis. SND1 is a known driver of hepatocellular carcinoma, but it is unknown if the Tudor domain is needed to drive this disease. We sought to identify the biological role of the SND1 Tudor domain in normal and tumorigenic settings. To do so, we developed two genetically engineered SND1 mouse models, namely a knockout (Snd1 KO) and a Snd1 Tudor domain mutated (Snd1 KI) mouse. Transcriptome analysis of normal KO and KI liver samples reveals a role for the SND1 Tudor domain in regulating expression of major acute phase proteins (APPs) and genes involved in the unfolded protein response (UPR), which could provide mechanistic insight into SND1’s functions in a tumor setting. These processes may provide insight into how SND1 functions as an oncogene. These results support the use of PRMT5 inhibitors, and the development of small molecule inhibitors that target the SND1 Tudor domain, as novel treatments for HCC.
2024-09-07 | GSE237559 | GEO
Project description:SND1 and its partner MTDH promote cancer and therapeutic resistance; however, the mechanisms responsible for their function and potential cooperation with other oncogenes are not completely understood. We report here that oncoprotein ERG binds to the SND1/MTDH protein complex via the Tudor domain of SND1. ERG is an ETS-domain transcriptional factor, which is recombined and overexpressed in approximately half of human prostate cancers. siRNA-mediated knockdowns and CRISPR-Cas9-mediated knockout of SND1 in human prostate epithelium cell lines revealed a critical role of SND1 in proliferation of ERG-overexpressing prostate epithelial cells. Transcriptional analysis of ERG-positive human prostate cancer cells demonstrated significant overlap between genes regulated by ERG and SND1. Mechanistically, we found that ERG promoted nuclear localization of SND1/MTDH. Significantly, forced nuclear localization of SND1 by addition of exogenous nuclear localization sequences (NLS) prominently increased its growth promoting function irrespective of the status of ERG expression. To determine if SND1 is necessary for prostate cancer tumorigenesis in vivo, we generated mice with prostate-epithelium-specific deletion of Snd1. We found that inactivation of Snd1 did not impact normal prostate gland homeostasis. However, prostate epithelium-specific deletion of Snd1 in autochthonous mouse model of prostate cancer (PB-Cre/ERG/PTENflox/flox mice) showed greatly reduced invasive cancer growth and tumor burden. Moreover, gene expression analysis revealed a significant overlap between in vivo prostate transcriptional signatures of ERG and Snd1. We conclude that SND1 plays a critical role in prostate tumorigenesis and targeting SND1 may represent a potential therapeutic target in prostate cancer.
2023-09-11 | GSE212840 | GEO
Project description:This study was to find genes directly regulated by SND1 and VND7. SND1XVE- or VND7XVE-expressing cells were treated with cycloheximide alone (control) or with cycloheximide plus estradiol (experimental) to identify genes directly activated by SND1 or VND7.
2011-07-31 | E-GEOD-23555 | biostudies-arrayexpress
Project description:Staphylococcal nuclease domain-containing protein 1 (SND1) is overexpressed in human hepatocellular carcinoma (HCC) and positively regulates development and progression of HCC. We established stable clones expressing SND1 shRNA in QGY-7703 cells and analyzed the gene expression profiles of a control clone and two SND1 knockdown clones to check what genes are regulated by SND1. Steady-state proliferating cells were collected for RNA extraction and Affymetrix microarray hybridization. Three biological replicates each of a control clone and 2 SND1 knockdown clones.
2013-04-01 | E-GEOD-44601 | biostudies-arrayexpress
Project description:PyMT tumor cells with indicated status of Mtdh and Snd1 were treated with camptothecin (CPT) and the transcirptome profiles were determined and compared two sets of experiments: (1) vector control vs Snd1-KD under CPT treament (2) PyMT/Mtdh-KO cells reconstituted with either WT or Snd1-binding deficient mutant Mtdh (W391D) under CPT treatment
2014-08-12 | E-GEOD-55522 | biostudies-arrayexpress
Project description:The RNA-binding protein Snd1 can regulate gene expression through various mechanisms, including microRNA decay. Here we have investigated microRNA expression in livers of WT and Snd1 knockout (KO) mice
2020-01-28 | GSE144309 | GEO
Project description:We have mapped m6A sites and endogenous SND1 binding sites in the viral and cellular transcriptome using TREx BCBL1-Rta cells. In addition, we have depleted SND1 in TREx BCBL1-Rta cells and BCBL1 cells and analyzed their RNA expression profile both during latency and lytic replication.
2019-10-15 | GSE119026 | GEO