Expression data from U251 RSK1 Knockout and RSK2 Knockout cell lines
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA881724 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The 90 kDa ribosomal S6 kinases (RSKs) are serine threonine kinases comprising four isoforms. The isoforms can have overlapping functions in regulation of migration, invasion, proliferation, survival, and transcription in various cancer types. We delineate RSK isoform-specific transcriptional gene regulation by comparing transcription programs in RSK1 and RSK2 knockout cells using microarray analysis.
2022-09-19 | GSE213592 | GEO
Project description:The p90 ribosomal S6 kinase (RSK) family, downstream targets of Ras/ERK signaling, encompass four human isoforms (RSK1-4). Glioblastoma (GBM) predominantly expresses RSK1 and RSK2. Notably, RSK1 is markedly upregulated in a subset of GBMs associated with dismal prognosis and immune infiltration, whereas RSK2 expression remains consistent across cases. We verified that GBM-derived cell lines recapitulate RSK isoform expression profiles and estimated their stoichiometry. Through the generation of RSK1 and RSK2 knockout (RSK1KO and RSK2KO) as well as double knockout (DKO) GBM cells, we investigated isoform-specific functions of RSK. Surprisingly, contrary to conventional belief, we found that mTORC1 is not activated by RSK isoforms. Instead, eIF4B phosphorylation at S422 was RSK-dependent rather than mTORC1/S6K-dependent, with RSK1 exerting a more pronounced effect. Intriguingly, RSK1 and RSK2 displayed differential effects on translation, with RSK1 maintaining translation of specific mRNAs under conditions of reduced overall translation due to mTORC1 inhibition, unlike RSK2. Finally, we verified that while the translatome of RSK1KO cells show a downregulation of mRNAs affecting cell cycle, DNA replication and repair, RSK2 depletion impacted mitochondrial and respiratory genes. Notably, DKO cells exhibited compounded phenotypes, underscoring the existence of isoform-specific gene regulation programs orchestrated by RSK. Collectively, our findings offer mechanistic insights crucial for unraveling the role of RSK1 in GBMs.
2025-06-25 | GSE263893 | GEO
Project description:The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked monogenic disease associating severe learning deficit andassociated to typical facial and digital abnormalities and skeletal changes. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized. In this study we explore, through X-Ray microtomographic analysis, the variable craniofacial dysmorphism and dental anomalies present in Rsk2 knockout mice, an animal model of Coffin-Lowry syndrome, as well as in triple Rsk1,2,3 knockout mutants. We report in these mutants the occurrence of a surpernumerary tooth mesial to the first molar. This highly penetrant phenotype is considered as a remnant of evolutionary lost teeth. This possibly leads to the significant reduction of the maxillary diastema. Abnormalities of molar shape were almost restricted to the mesial part of both upper and lower first molars (M1). We also report an expression analysis of the four Rsk genes (Rsk1, 2, 3 and 4) at various stages of odontogenesis in wild-type (WT) mice. Rsk2 was mainly expressed in the mesenchymal, neural crest derived compartment, correlating with proliferative areas of the developing teeth and consistent with a biological function of RSK2 in cell cycle control and cell growth, which when invalidated could be responsible for the dental phenotype. In an attempt to unravel the molecular pathways involved in the genesis of these dental defects, we performed a comparative transcriptomic (DNA microarray) analysis of mandibular wild-type versus Rsk2-/Y molars, and further demonstrated a misregulation of selected genes, using a Rsk2 shRNA knock-down strategy in molar tooth germs cultured in vitro.
2014-01-13 | E-GEOD-51034 | biostudies-arrayexpress
Project description:The p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase (ERK) signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 (mTORC1) pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in non-tumoral brain (NB) and grade I-IV gliomas. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBMs demonstrating the lowest RSK3 protein levels. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (RSK1hi) that excluded long-survivor cases expressed higher levels of RSK1. No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in glioblastomas (GBM) were associated with worse survival. RSK1hi and, to a lesser extent, RSK2hi GBMs, showed higher levels of phosphorylated RSK, which indicates RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated-natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long-survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker LAPTM5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration, suggests RSK1 as a potential progression marker and therapeutic target for gliomas.
2019-10-26 | GSE139380 | GEO
Project description:RSK2 is a serine/threonine kinase downstream signaling mediator in the RAS/ERK signaling pathway and may be a therapeutic target in mantle cell lymphoma (MCL). RSK2-Ser227 in the N-terminal kinase domain (NTKD) of RSK2 was found to be ubiquitously active in five MCL-derived cell lines and in tumor tissues derived from five MCL patients. BI-D1870, an inhibitor specific to RSK2-NTKD, caused RSK2-Ser227 dephosphorylation, and thereby, induced dose-dependent growth inhibition via G2/M cell cycle blockade and apoptosis. Comparative gene expression profiling of the MCL-derived cell lines showed that inhibition of RSK2-Ser227 by BI-D1870 caused downregulation of oncogenes, such c-MYC and MYB; anti-apoptosis genes, such as BCL2 and BCL2L1; genes for B cell development, including IKZF1, IKZF3 and PAX5; and genes constituting the B cell receptor signaling pathway, such as CD19, CD79B and BLNK. These findings show that targeting of RSK2-Ser227 enables concomitant blockade of pathways that are critically important in B cell tumorigenesis.
2020-03-25 | GSE147484 | GEO
Project description:We showed that DBTRG is more invasive than U251 cell lines by novel brain-stiffness-mimicking matrix gel invasion platform and transwell invasion assay. To understand the molecular mechanisms of DBTRG being more invasive than U251, we performed transcriptomic sequencing analysis of DBTRG and U251 cell lines.
2022-04-18 | GSE200574 | GEO
Project description:Two CTCF-binding sites (CTCF-A and CTCF-B) might mediate frequent chromatin interactions in the 11p11.2 locus and contribute to the co-regulation of genes within the 11p11.2 locus. In order to verify whether knockout of these CTCF-binding sites could influence expression of genes in the 11p11.2 locus, and explore the subsequent consequences of the knockout, we knocked out two CTCF-binding sites (CTCF-A and CTCF-B) in U251 cell with a stable expression of mutant APP 128 (M671L) (U251-APP cells). RNA-seq (by IlluminaHiseq 4000) and following analyses were then performed to detect genes whose expression were influenced by CTCF-binding sites knockout.
2025-12-31 | GSE173328 | GEO
Project description:The amine oxidase LOXL3 has been implicated in tumor development and progression, with elevated expression in glioblastoma (GBM). This enzyme influences GBM cell adhesion, migration, and proliferation, and is demonstrated correlation with tubulin expression. Microtubules, as the major component of the cytoskeleton, are crucial for cell cycle and mitotic progression. In this study, LOXL3 knockout was performed using CRISPR-Cas9 in two GBM cell lines, U87MG and U251, to achieve high silencing efficiency. The knockdown resulted in decreased cell viability in both cell lines. Transcriptome enrichment analysis of U87MG cells revealed downregulation of genes associated to tubulin acetylation, which was subsequently confirmed by Western blot analysis. Both U87MG and U251 cells exhibited downregulation of cell cycle and proliferation-related genes. Functional assays confirmed that LOXL3-knockout cells exhibited delayed cell cycle progression and significant alterations in mitotic spindles during metaphase-anaphase transition. Nuclear analysis revealed morphological changes indicative of mitotic catastrophe in U87MG cells and senescence in U251 cells. Additionally, LOXL3-knockout clones displayed reduced cell adhesion and migration. Interestingly, LOXL3 knockdown in GBM cell lines reduces tubulin acetylation, leading to mitotic catastrophe and subsequent cell death in a TP53 mutation-dependent manner. These findings highlight the potential of targeting LOXL3 as a combinatory strategy for advancing research and developing novel therapeutic approaches in TP53-mutated GBM.
2026-01-22 | GSE288138 | GEO
Project description:We used CRISPR RSK2 knock-out MCF-7 cells to identify RSK2-regulated genes.
2020-06-01 | GSE99707 | GEO
Project description:To investigate the function of COL8A1 in GSCs progression, we established U251-COL8A1 cell lines with COL8A1 overexpressed. Then we performed gene expression profiling analysis using data obtained from RNA-seq of 2 cells (U251NC and U251-COL8A1)
2024-07-01 | GSE246528 | GEO