Transcriptome Analysis of Signaling Pathways Targeted by Ellagic Acid in Hepatocellular Carcinoma Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171311 | GEO | 2021/04/02
REPOSITORIES: GEO
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2023-07-18 | GSE233817 | GEO
Project description:Background: Acute diarrhea is still a common and serious disease. The causes of acute diarrhea are very complicated. Therefore, we need to find a medicine to control diarrhea symptoms, save time for diagnosis of pathogens, and prevent drug abuse. Ellagic acid (EA), a natural polyphenol drug, has anti-diarrhea effects. However, the action mechanisms of EA for non-specific diarrhea have not been characterized. Materials and methods: To study the mechanisms of EA, mice were divided into four groups (group C were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml physiological saline, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group D were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group E were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Group V were intraperitoneally injected with 0.1ml GW9662 (1m g/ml) and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml).) Transcriptome were performed on ileum tissues of mice in group D and E. Histological examination and qRT-PCR were performed on ileum tissues of mice in group C, D, E and V. Results: We found that a total of 273 differentially expressed genes (DEGs) were obtained, including 160 up-regulated DEGs and 113 down-regulated DEGs. The DEGs were enriched in 458 Gene Ontology (GO) terms and 15 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. The peroxisome proliferator activated receptor (PPAR) signaling pathway was the most significantly enriched in KEGG pathways. We used the PPAR-specific antagonist GW9662 to validate the anti-diarrhea and anti-inflammatory effect of EA in group V compared with group E. Conclusively, EA protected ileums against castor oil-induced inflammation and diarrhea by activating the PPAR signaling pathway and a method was used to study the mechanism of EA.
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Project description:Cell size and the cell cycle are intrinsically coupled and abnormal increases in cell size are associated with senescence and permanent cell cycle arrest. The mechanism by which overgrowth primes cells to withdraw from the cell cycle remains unknown. We investigate this here using CDK4/6 inhibitors that arrest cell cycle progression during G0/G1 and are used in the clinic to treat ER+/HER2- metastatic breast cancer. We demonstrate that CDK4/6 inhibition promotes cellular overgrowth during G0/G1, causing p38MAPK-p53-p21-dependent cell cycle withdrawal. We find that cell cycle withdrawal is triggered by two waves of p21 induction. First, overgrowth during a long-term G0/G1 arrest induces an osmotic stress response. This stress response produces the first wave of p21 induction. Second, when CDK4/6 inhibitors are removed, a fraction of cells escape long term G0/G1 arrest and enter S-phase where overgrowth-driven replication stress results in a second wave of p21 induction that causes cell cycle withdrawal from G2, or the subsequent G1. We propose a model whereby both waves of p21 induction contribute to promote permanent cell cycle arrest. This model could explain why cellular hypertrophy is associated with senescence and why CDK4/6 inhibitors have long-lasting effects in patients.
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Project description:In this study, we assessed the effect of acute oral administration of ellagic acid on metabolic parameters, oxidative stress and transcriptomic profiles in an inbred rodent model, carrying a variant of one of the metabolic syndrome-related genes, Zbtb16 (Zinc Finger And BTB Domain Containing 16). Over a period of three weeks, adult male rats of the SHR-Lx/k.o. strain were fed a high-fat diet accompanied with daily intragastric gavage of ellagic acid (50 mg/kg body weight; HFD-EA rats) or solvent only (HFD rats). At the end of the protocol, morphometric and metabolic parameters, including glucose tolerance test, serum lipid concentration and oxidative stress markers along with transcriptomic profile of liver, brown, and epididymal adipose tissues were assessed.
2021-02-19 | E-MTAB-8928 | biostudies-arrayexpress
Project description:Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclearly. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent non-tumorous tissues and cell lines. The effect of SNHG17 on proliferation, migration and apoptosis of HCC were investigated by knockdown and overexpressing SNHG17 in HCC cell lines. RNA sequencing was utilized to explore the underlying mechanism. Utilizing publicly available TCGA-LIHC, GSE102079 HCC datasets and qRT-PCR, we found SNHG17 was significantly upregulated in HCC tissues and cell lines and was notably associated with larger tumor size, poorly differentiation, presence of vascular invasion and advanced TNM stage. Furthermore, gain- and loss-of-function studies demonstrated that SNHG17 promoted cell proliferation, migration and inhibited apoptosis of HCC. By employing RNA sequencing, we found knockdown of SNHG17 caused 1037 differentially expressed genes, highly enriched in several pathways, including metabolic, PI3K-Akt, cell adhesion, regulation of cell proliferation and apoptotic pathway, among them 92 were overlapped with SNHG17-related genes in TCGA-LIHC dataset. Furthermore, ERH, TBCA, TDO2 and PDK4 were successfully validated and found significantly dysregulated in HCC tissues. Moreover, HCC patients with higher SNHG17 expression had a relatively poor overall survival and disease-free survival and ERH, PDK4 also played markedly role in prognosis of HCC. Broadly, our findings illustrate that SNHG17 acts as a noncoding oncogene in HCC progression, suggesting its potential value as a novel target for HCC therapy.
2021-09-12 | GSE152256 | GEO
Project description:RNA-seq is a powerful tool for comprehensive characterization of whole transcriptome at both gene and exon levels and with a unique ability of identifying novel splicing variants. To date, RNA-seq analysis of HBV-related HCC has not been reported. In this study, we performed transcriptome analyses for 10 matched pairs of cancer and non-cancerous tissues from Chinese HBV-related hepatocelluar carcinoma patients using 36bp single-end sequencing approach on Solexa/Illumina GAII platform. On average, about 21.6 million sequencing reads and 10.6 million aligned reads were obtained for samples sequenced on each lane, which was able to identify > 50% of all the annotated genes for each sample. Furthermore, from by far the largest database of transcripts expressed in HCC tissues, we identified 1,378 significantly differently expressed genes (DEGs) and 24, 338 differentially expressed exons (DEEs). Comprehensive function analyses indicated that cell growth-related, metabolism-related and immune-related pathways were most significantly enriched by DEGs, pointing to a complex mechanism for HCC carcinogenesis. Positional gene enrichment analysis showed that DEGs were most significantly enriched at chromosome 8q21.3-24.3. The most interesting findings were from the analysis at exon levels where we characterized three major patterns of expression changes between gene levels and exon levels, implying a much complex landscape of transcript-specific differential expressions in HCC. Finally, we identified a novel highly up-regulated exon-exon junction in ATAD2 (ATPase family, AAA domain containing 2) gene in HCC tissues. Overall, to our best knowledge, our study represents the most comprehensive characterization of the HBV-related HCC transcriptome including exon level expression changes and novel splicing variants, which illustrated the power of RNA-seq and provided important clues for understanding the molecular mechanisms of HCC pathogenesis at system-wide levels. A comprehensive analysis of transcriptome for 10 match-paired HBV-related Chinese HCC and non-cancerous adjacent tissues. Processed data files: Exon-level results, gene-level results, differentially expressed exons, and differently expressed genes (DEGs).
2013-11-24 | E-GEOD-25599 | biostudies-arrayexpress
Project description:Barr2017 - Dynamics of p21 in hTert-RPE1
cells
This deteministic model reveals that a
bistable switch created by Cdt2, promotes irreversible S-phase
entry by keeping p21 levels low, prevents premature S-phase exit
upon DNA damage
This model is described in the article:
DNA damage during S-phase
mediates the proliferation-quiescence decision in the
subsequent G1 via p21 expression.
Barr AR, Cooper S, Heldt FS, Butera
F, Stoy H, Mansfeld J, Novák B, Bakal C.
Nat Commun 2017 Mar; 8: 14728
Abstract:
Following DNA damage caused by exogenous sources, such as
ionizing radiation, the tumour suppressor p53 mediates cell
cycle arrest via expression of the CDK inhibitor, p21. However,
the role of p21 in maintaining genomic stability in the absence
of exogenous DNA-damaging agents is unclear. Here, using live
single-cell measurements of p21 protein in proliferating
cultures, we show that naturally occurring DNA damage incurred
over S-phase causes p53-dependent accumulation of p21 during
mother G2- and daughter G1-phases. High p21 levels mediate G1
arrest via CDK inhibition, yet lower levels have no impact on
G1 progression, and the ubiquitin ligases CRL4Cdt2 and SCFSkp2
couple to degrade p21 prior to the G1/S transition.
Mathematical modelling reveals that a bistable switch, created
by CRL4Cdt2, promotes irreversible S-phase entry by keeping p21
levels low, preventing premature S-phase exit upon DNA damage.
Thus, we characterize how p21 regulates the
proliferation-quiescence decision to maintain genomic
stability.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000660.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
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Public Domain Dedication for more information.
2016-06-09 | BIOMD0000000660 | BioModels
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Project description:Mouse Embryonic Stem Cells (ESCs) grown in serum-supplemented conditions are characterized by an extremely short G1-phase due to the lack of G1-phase control. Concordantly, the G1-phase-specific P53-P21 pathway is compromised in serum ESCs. Here we provide evidence that P53 is activated upon transition of serum ESCs to their pluripotent ground state using serum-free 2i conditions and modulates G1-phase progression. Our data shows that the elongated G1-phase characteristic of ground state ESCs is dependent on P53. RNA-seq and ChIP-seq analyses reveal that P53 directly regulates the expression of the Retinoblastoma (RB) protein and that the hypo-phosphorylated, active RB protein plays a key role in G1-phase control. Our findings suggest that the P53-P21 pathway is active in ground state 2i ESCs and that its role in the G1-checkpoint is abolished in serum ESCs. Taken together, the data reveals a mechanism by which inactivation of P53 can lead to loss of RB and uncontrolled cell proliferation.
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