Genome-wide analysis of SIK2 regulated genes and pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45711 | GEO | 2015/01/12
SECONDARY ACCESSION(S): PRJNA195915
REPOSITORIES: GEO
Similar Datasets
Project description:Identification of SIK2 regulated genes and pathways after SIK2 knock-down and overexpression of a wild-type and kinase-dead SIK2. The hypothesis is that SIK2 regulated gene expression via CREB1 Total RNAs were obtained after SIK2 gene was knocked down with siRNA and after a wild-type SIK2 or a kinase-dead SIK2 construct were over-expressed in LNCaP cells. A control where the cells were treated with a CREB1 inducer (Forskolin) was also included.
2015-01-12 | E-GEOD-45711 | biostudies-arrayexpress
Project description:The phosphorylation state of human HA-tagged-SIK2, adenovirally introduced in murine hepatocytes (C57/BL/6 strain) was analysed in unstimulated and in response to glucagon- or insulin- treated conditions. Background:- LKB1 is a master kinase that regulates metabolism and growth through AMPK and 12 other closely-related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. The salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressor downstream of LKB1 in the liver. A selective SIK inhibitor (HG-9-91-01) promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive-mutant-SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation/activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver.
2014-08-08 | PXD001032 | Pride
Project description:HeLa cells transfected with non-targeting control- and anti-SIK2 siRNA were left uninfected or infected with Salmonella and lysed 30 min pi. Following tryptic-digest peptides were labeled using TMT-pro 16-plex and phosphopeptides enriched. The endogenously tagged SIK2-HA IP workflow. Hela wild type or endogenous SIK2-HA-tagged HeLa cells were left uninfected or infected with Salmonella and lysed 1 h post-infection, followed by HA-IP, Tryptic digest, TMT-labeling and LC-MS/MS analysis.
2021-05-06 | PXD021859 | Pride
Project description:Currently, there are no orally available bone anabolic therapies to treat osteoporosis. Intermittent parathyroid hormone injections stimulate bone formation through a signaling pathway that inhibits the actions of salt inducible kinase (SIK) isoforms 2 and 3. Therefore, direct small molecule SIK2/SIK3 inhibitors represent a promising treatment strategy to mimic PTH actions. Here we tested GLPG3970, a potent and selective SIK2/SIK3 inhibitor developed for clinical use in inflammatory diseases, in rodent models of post-menopausal osteoporosis. In bone cells, GLPG3970 reduces phosphorylation levels of SIK substrates and regulates gene expression patterns, as assessed by RNA-sequencing, in a PTH-like manner. GLPG3970 was administered to female mice and rats rendered hypogonadal via surgical oophorectomy (OVX) via twice daily oral gavage. In parallel, separate groups of rodents were treated with once daily subcutaneous PTH injections. Skeletal endpoints, serum bone turnover markers, micro-CT, histomorphometry, and mechanical testing, were assessed after study termination. In both OVX-operated mice and rats, GLPG3970 treatment increased markers of bone formation and cancellous bone mass, and increased rat vertebral body bone strength. These results provide strong justification for further development of orally available SIK2/SIK3 inhibitors to treat post-menopausal osteoporosis.
2025-09-01 | GSE285777 | GEO
Project description:Metastatic uveal melanomas are highly resistant to all existing treatments. To address this critical issue, we performed a genome-wide CRISPR-Cas9 knockout screen, which revealed the LKB1-SIK2 module in restraining uveal melanoma tumorigenesis. Functionally, LKB1 loss enhances proliferation and survival through SIK2 inhibition and up-regulation of the sodium/calcium (Na+/Ca2+) exchanger SLC8A1. This signalling cascade promotes increased level of intracellular calcium and mitochondrial reactive oxygen species, two hallmarks of cancer. We further demonstrate that combination of an SLC8A1 inhibitor and a mitochondria-targeted antioxidant promotes enhanced cell death efficacy in LKB1- and SIK2-negative uveal melanoma cells compared to control cells. We also designed an LKB1-deficient prognostic gene signature of patient survival that may be predictive of response to this combination. Our data thus identify not only metabolic vulnerabilities, but also new prognostic markers, thereby providing a therapeutic strategy for particular subtypes of metastatic uveal melanoma.
2024-05-25 | GSE233458 | GEO
Project description:Purpose: Analysis of the regulatory network involved in SIK2 in breast cancer cells activated by the Wnt/β-catenin pathway. Methods: mRNA profiles of BT549-shSIK2 and BT549-Scrambled group that Wnt3a treated for 2 hours were generated by deep sequencing, using Illumina Novaseq platform. Index of the reference genome was built using Hisat2 v2.0.5 and paired-end clean reads were aligned to the reference genome using Hisat2 v2.0.5. featureCounts v1.5.0-p3 was used to count the reads numbers mapped to each gene. And then FPKM of each gene was calculated based on the length of the gene and reads count mapped to this gene. Differential expression analysis of two conditions/groups (two biological replicates per condition) was performed using the DESeq2 R package (1.16.1). The resulting P-values were adjusted using the Benjamini and Hochberg’s approach for controlling the false discovery rate . Genes with an adjusted P-value <0.05 found by DESeq2 were assigned as differentially expressed. Clusterprofiler software was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis of the differential gene sets. Results: We identified 1709 differential genes, of which 1147 were up-regulated and 562 were down-regulated. In GO enrichment analysis, the biological process is mainly in the cell ions homeostasis, the cell components are mainly enriched on the cell surface, and the molecular function is mainly in the transmembrane signaling receptor activity. KEGG analysis shows that differential genes are enriched in Axon guidance and Nicotinate and nicotinamide metabolism pathways. Conclusion: Based on RNA-seq analysis, the regulatory network involved in SIK2 in breast cancer response to Wnt signaling is depicted.
2021-03-24 | GSE169344 | GEO
Project description:To screen the genes and pathways regulated by CREB1 in the THP1 monocytes induced by LPS, THP1 monocytes were transfected by CREB1 shRNA and then treated by LPS for 3 hours.
2023-04-14 | GSE229580 | GEO
Project description:Genes regulated by CREB1 in LPS-primed THP1 monocytes
| PRJNA955033 | ENA
Project description:RNA-seq analysis of BT549 cells based on SIK2 knockdown
| PRJNA716309 | ENA
Project description:Various physiological stimuli, such as cold environment, diet, and hormones, trigger brown adipose tissue (BAT) to produce heat through sympathetic nervous system (SNS)- and -adrenergic receptors (ARs). The AR stimulation increases intracellular cAMP levels through heterotrimeric G proteins and adenylate cyclases, but the processes by which cAMP modulates brown adipocyte function are not fully understood. Here we described that specific ablation of cAMP production in brown adipocytes led to reduced lipolysis, mitochondrial biogenesis, uncoupling protein 1 (Ucp1) expression, and consequently defective adaptive thermogenesis. Elevated cAMP signaling by sympathetic activation inhibited Salt-inducible kinase 2 (Sik2) through protein kinase A (PKA)-mediated phosphorylation in brown adipose tissue. Inhibition of SIKs enhanced Ucp1 expression in differentiated brown adipocytes and Sik2 knockout mice exhibited enhanced adaptive thermogenesis at thermoneutrality in an Ucp1-dependent manner. Taken together, our data indicate that suppressing Sik2 by PKA-mediated phosphorylation is a requisite for SNS-induced Ucp1 expression and adaptive thermogenesis in BAT, and targeting Sik2 may present a novel therapeutic strategy to ramp up BAT thermogenic activity in humans.
2018-07-12 | PXD009262 | Pride