LncRNA-LPE binding to TCP1 activates the PI3K/AKT signaling pathway in preeclampsia
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ABSTRACT:
PROVIDER: PRJNA1138706 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29914812_1.fastq.gz | Fastqsanger.gz | |||
| SRR29914812_2.fastq.gz | Fastqsanger.gz | |||
| SRR29914813_1.fastq.gz | Fastqsanger.gz | |||
| SRR29914813_2.fastq.gz | Fastqsanger.gz | |||
| SRR29914814_1.fastq.gz | Fastqsanger.gz |
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Project description:The role of long noncoding RNA (LncRNA) in numerous diseases was well-established. However, its pathological significance in preeclampsia (PE) remains obscure. In this investigation, a novel low-expression LncRNA (LncRNA-LPE) was identified in PE, and the regulatory mechanism in the progression of PE was examined. We found that LncRNA-LPE was downregulated in PE compared with normal plancenta, suggesting its potential relation with the development of PE. Modulation of LncRNA-LPE expression in trophoblast cells revealed its capacity to influence the migration and invasion abilities. To identify proteins that interact with LncRNA-LPE, RNA pull-down assays, mass spectrometry, and RNA immunoprecipitation (RIP) assays were employed. And we found LncRNA-LPE could interact with the RNA-binding protein T-complex protein 1 (TCP1), which might subsequently influence the PI3K/AKT signaling pathway and lead to autophagy changing. Our results demonstrated that LncRNA-LPE facilitates the development of preeclampsia by binding to TCP1 and activating PI3K/AKT signaling pathway, indicating its potential as a morbidity marker and therapeutic target for preeclampsia.
2024-07-26 | GSE272773 | GEO
Project description:Background: Excessive or inappropriate radiation exposure can cause serious damage to organisms. Radiation-induced thymus injury (RITI) is a serious complication associated with radiation and is mediated by RNAs. Methods: The thymus tissues of mice were analyzed using RNA-sequencing (RNA-seq) and their libraries 24 h after exposure to 6 Gy of X-ray radiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and miRNA-based mRNAs were predicted after irradiation to develop the lncRNA-miRNA-mRNA ceRNA axis. Results: The results revealed that after irradiation, 6214 mRNAs, 160 miRNAs, and 1999 lncRNAs were significantly upregulated while 2676 mRNAs, 165 miRNAs, and 941 lncRNAs were considerably downregulated. Angiogenesis and ameboidal-type cell migration for Biological Process; actin cytoskeleton and extracellular matrix (ECM) for Cellular Component; and actin binding and ECM structural component for Molecular Function represent the most prominent changes in GO analysis function. A total of 333 cellular function were significantly altered by PTEN, while 175 CFs were substantially changed by PDPK1. Pathways involved in cancer, ECM-receptor interaction, focal adhesion, axon guidance, PI3K-AKT signaling, and adrenal signaling in cardiomyocytes were identified via KEGG pathway analysis. For experimental confirmation, the crucial pathway PI3K-AKT was selected to have a role in thymus degeneration after radiation exposure. Conclusion: A lncRNA-miRNA-mRNA ceRNA axis of RITI was successfully developed in a mouse model after irradiation. The PI3K-AKT pathway contributes to preventing radiation-induced cell death in RITI, and the differentially expressed RNA in the initial stage of this injury may result in serious consequences.
2025-01-13 | GSE285844 | GEO
Project description:Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN. For each sample, 500 ng of total RNA were used to synthesize biotinylated cRNA with Illumina RNA Amplification Kit (Ambion, Austin, TX). Synthesis was carried out according to the manufacturersâ instructions. From each sample, technical triplicates were produced and 750 ng cRNA were hybridized for 18h to Human HT-12_V3_0_R1 Expression BeadChips (Illumina, San Diego, CA). Hybridized chips were washed and stained with streptavidin-conjugated Cy3 (GE Healthcare, Milan, Italy). BeadChips were dried and scanned with an Illumina Bead Array Reader (Illumina).
2016-12-01 | E-MTAB-5286 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE35701: CP001: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy GSE35703: CP003: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy Refer to individual Series
2012-07-21 | E-GEOD-35705 | biostudies-arrayexpress
Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Affymetrix U133 Plus 2.0 profiling of SY5Y-TetR-FOXO3A cells treated with doxycycline and/or the PI3K/mTOR inhibitor PI-103. Each condition profiled in triplicate.
2013-05-01 | E-GEOD-42762 | biostudies-arrayexpress
Project description:Background: Excessive or inappropriate radiation exposure can cause serious damage to organisms. Radiation-induced thymus injury (RITI) is a serious complication associated with radiation and is mediated by RNAs. Methods: The thymus tissues of mice were analyzed using RNA-sequencing (RNA-seq) and their libraries 24 h after exposure to 6 Gy of X-ray radiation. The target mRNAs were functionally annotated and the target lncRNA-based miRNAs and miRNA-based mRNAs were predicted after irradiation to develop the lncRNA-miRNA-mRNA ceRNA axis. Results: The results revealed that after irradiation, 6214 mRNAs, 160 miRNAs, and 1999 lncRNAs were significantly upregulated while 2676 mRNAs, 165 miRNAs, and 941 lncRNAs were considerably downregulated. Angiogenesis and ameboidal-type cell migration for Biological Process; actin cytoskeleton and extracellular matrix (ECM) for Cellular Component; and actin binding and ECM structural component for Molecular Function represent the most prominent changes in GO analysis function. A total of 333 cellular function were significantly altered by PTEN, while 175 CFs were substantially changed by PDPK1. Pathways involved in cancer, ECM-receptor interaction, focal adhesion, axon guidance, PI3K-AKT signaling, and adrenal signaling in cardiomyocytes were identified via KEGG pathway analysis. For experimental confirmation, the crucial pathway PI3K-AKT was selected to have a role in thymus degeneration after radiation exposure. Conclusion: A lncRNA-miRNA-mRNA ceRNA axis of RITI was successfully developed in a mouse model after irradiation. The PI3K-AKT pathway contributes to preventing radiation-induced cell death in RITI, and the differentially expressed RNA in the initial stage of this injury may result in serious consequences.
2025-01-13 | GSE285845 | GEO
Project description:Background—YAP, the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEAD sequence specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyocyte proliferation and survival. However, the direct transcriptional targets through which YAP exerts its effects are poorly defined. Methods and Results—To identify genes directly regulated by YAP in cardiomyocytes, we combined differential gene expression analysis in YAP gain- and loss-of-function with genome-wide identification of YAP bound loci using chromatin immunoprecipitation and high throughput sequencing. This screen identified Pik3cb, encoding p110β, a catalytic subunit of phosphoinositol-3-kinase (PI3K), as a candidate YAP effector that promotes cardiomyocyte proliferation and survival. We validated YAP and TEAD occupancy of a conserved enhancer within the first intron of Pik3cb, and show that this enhancer drives YAP-dependent reporter gene expression. Yap gain- and loss-of-function studies indicated that YAP is necessary and sufficient to activate the PI3K-Akt pathway. Like Yap, Pik3cb gain-of-function stimulated cardiomyocyte proliferation, and Pik3cb knockdown dampened the YAP mitogenic activity. Reciprocally, Yap loss-of-function impaired heart function and reduced cardiomyocyte proliferation and survival, all of which were significantly rescued by AAV-mediated Pik3cb expression. Conclusion—Pik3cb is a crucial direct target of YAP, through which the YAP activates PI3K-AKT pathway and regulates cardiomyocyte proliferation and survival. Yap wild type ChIPseq and input
2015-02-20 | E-GEOD-57717 | biostudies-arrayexpress
Project description:Our Prior research has shown that 6-hydroxygenistein (6-OHG) alleviates hypobaric hypoxia induced brain injury (HHBI) achieved by its powerful antioxidant, anti-inflammatory, and anti-apoptotic capabilities, but its mechanism still requires additional investigation. The objective of this study was to uncover the protective mechanism of 6-OHG against HHBI based on transcriptomics analysis and experimental validation.The RNA-Seq analysis revealed 1585 differentially expressed genes (DEGs) between the Con and Mod groups, with 460 upregulated and 1125 downregulated. Between the 6-OHG and Mod groups, there were 679 DEGs, including 348 upregulated and 331 downregulated genes. Go and KEGG function analyses highlighted the PI3K/AKT signaling pathway as a crucial regulatory mechanism. Western blot analysis showed that HH exposure caused a decrease in the ratios of p-PI3K/PI3K and p-AKT/AKT in the mouse brain, but this effect was reversed by 6-OHG treatment, indicating that 6-OHG activates the PI3K/AKT signaling pathway. Furthermore, LY294002, a selective PI3K inhibitor, effectively blocked this activation and also abolished the protective effects of 6-OHG on histopathological damage, as well as its antioxidant, anti-inflammatory, and anti-apoptotic activities in HHBI mice. In summary, 6-OHG mitigates HHBI by activating the PI3K/AKT signaling pathway, suggesting its potential therapeutic application for HHBI treatment.
2025-11-14 | GSE307180 | GEO
Project description:The phosphoinositide 3-kinase (PI3K) pathway integrates extracellular stimuli to phosphorylate and activate key downstream effectors such as AKT and serum-and glucocorticoid-inducible kinase (SGK1). We have previously reported that the PI3K pathway regulates ER-dependent transcription in breast cancer through the phosphorylation of the epigenetic regulator KMT2D by AKT. Here, we provide new insights into how the PI3K pathway propagates its effects to control KMT2D and ER function via SGK1, another PI3K downstream effector. Specifically, we show that PI3K inhibition, via a negative feedback loop, activates SGK1 to promote chromatin-based regulation of ER-dependent gene expression. PI3K/AKT inhibitors activate ER, which subsequently promotes SGK1 transcription through direct binding to its promoter. Elevated SGK1, in turn, phosphorylates KMT2D, suppressing its function and altering the chromatin landscape to attenuate ER-dependent expression. Thus, we have determined that SGK1 regulates the chromatin landscape and ER-dependent transcription via the direct phosphorylation of KMT2D. These findings reveal an ER-SGK1-KMT2D signaling circuit aimed to attenuate ER response through a previously unknown role for SGK1 to program chromatin and ER transcriptional output.
2019-04-02 | GSE119522 | GEO
Project description:Background—YAP, the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEAD sequence specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyocyte proliferation and survival. However, the direct transcriptional targets through which YAP exerts its effects are poorly defined. Methods and Results—To identify genes directly regulated by YAP in cardiomyocytes, we combined differential gene expression analysis in YAP gain- and loss-of-function with genome-wide identification of YAP bound loci using chromatin immunoprecipitation and high throughput sequencing. This screen identified Pik3cb, encoding p110β, a catalytic subunit of phosphoinositol-3-kinase (PI3K), as a candidate YAP effector that promotes cardiomyocyte proliferation and survival. We validated YAP and TEAD occupancy of a conserved enhancer within the first intron of Pik3cb, and show that this enhancer drives YAP-dependent reporter gene expression. Yap gain- and loss-of-function studies indicated that YAP is necessary and sufficient to activate the PI3K-Akt pathway. Like Yap, Pik3cb gain-of-function stimulated cardiomyocyte proliferation, and Pik3cb knockdown dampened the YAP mitogenic activity. Reciprocally, Yap loss-of-function impaired heart function and reduced cardiomyocyte proliferation and survival, all of which were significantly rescued by AAV-mediated Pik3cb expression. Conclusion—Pik3cb is a crucial direct target of YAP, through which the YAP activates PI3K-AKT pathway and regulates cardiomyocyte proliferation and survival. Two groups were involved in this study:TNTcreYapfl_het group and TNTcreYapfl_KO group. Each group contained three biological replicates. Embryo hearts were collected at E12.5 and dissociated. Cardiomyocytes were collected by FACS. The total RNA of cardiomyocytes were isolated for microarray analysis.
2015-02-20 | E-GEOD-57718 | biostudies-arrayexpress