Lower Concentrations of Blueberry Polyphenolic-Rich Extract Differentially Alter HepG2 Cell Proliferation and Expression of Genes Related to Cell-Cycle, Oxidation and Epigenetic Machinery

2012 ◽  
Vol 03 (01) ◽  
Author(s):  
Farideh Shafiee Kermani
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Hepg2 Cell ◽  
Expression Of Genes ◽  
Epigenetic Machinery

The Role of Retinoblastoma Protein in Cell Cycle Regulation: An Updated Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Rabih Roufayel ◽  
Rabih Mezher ◽  
Kenneth B. Storey
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Cycle Control ◽  
Expression Of Genes ◽  
E2f Transcription Factor ◽  
Cellular Energetics ◽  
Development And Differentiation ◽  
E2f Transcription Factors ◽  
Rb Phosphorylation

: Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provide a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.

scholarly journals Downregulated NORAD in neuroblastoma promotes cell proliferation via chromosomal instability and predicts poor prognosis

2020 ◽  
Author(s):  
Yongbo Yu ◽  
Feng Chen ◽  
Yaqiong Jin ◽  
Yeran Yang ◽  
Shengcai Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Chromosomal Instability ◽  
Clinical Samples ◽  
Advanced Tumor Stage ◽  
Expression Of Genes ◽  
Public Data ◽  
And Migration ◽  
Proliferation And Migration

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in neuroblastoma (NB) pathogenesis. The aim of this study was to elucidate the roles and underlying mechanism of non-coding RNA activated by DNA damage (NORAD) in childhood NB. Both public data and clinical specimens were used to determine NORAD expression. Colony formation, cell proliferation and wound healing assays were performed to evaluate NORAD effects on proliferation and migration of SH-SY5Y and SK-N-BE(2) cells. Flow cytometry was used to examine the cell cycle changes. The expression of genes and proteins involved in chromosomal instability was determined by qRT-PCR and western blotting, respectively. Our results showed that low NORAD expression correlated with advanced tumor stage, high risk and MYCN amplification in both public data and clinical samples. Kaplan–Meier analysis indicated that patients with low NORAD expression had poor survival outcomes. Functional research showed that NORAD knockdown promoted cell proliferation and migration, and arrested the cell cycle at the G2/M phase. Moreover, the expression of the DNA damage sensor, PARP1, increased after NORAD knockdown, indicating a potential contribution of NORAD to DNA damage repair. NORAD silencing also affected the expression of genes and proteins related to sister chromatid cohesion and segregation, which are involved in chromosomal instability and consequent aneuploidy. These results suggest that NORAD may serve as a tumor suppressor in NB pathogenesis and progression. Thus, NORAD is a potential therapeutic target and a promising prognostic marker for NB patients.

CPBMF65, a synthetic human uridine phosphorylase-1 inhibitor, reduces HepG2 cell proliferation through cell cycle arrest and senescence

2020 ◽  
Vol 38 (6) ◽  
pp. 1653-1663 ◽  
Author(s):  
Elisa Feller Gonçalves da Silva ◽  
Kelly Goulart Lima ◽  
Gabriele Catyana Krause ◽  
Gabriela Viegas Haute ◽  
Leonardo Pedrazza ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Hepg2 Cell ◽  
Uridine Phosphorylase ◽  
Cycle Arrest

scholarly journals Effects of Estrogen and Estrogen Receptors on Transcriptomes of HepG2 Cells: A Preliminary Study Using RNA Sequencing

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Minqian Shen ◽  
Jingyi Cao ◽  
Haifei Shi
Keyword(s):  
Cell Cycle ◽  
Liver Cancer ◽  
Rna Sequencing ◽  
Hepg2 Cell ◽  
Estrogen Receptor Alpha ◽  
Chemical Carcinogenesis ◽  
Protective Effects ◽  
Metabolic Processes ◽  
Go Analysis ◽  
Expression Of Genes

Men have a much higher incidence of hepatocellular carcinoma (HCC), the predominant form of liver cancer, than women, suggesting that estrogens play a protective role in liver cancer development and progression. To begin to understand the potential mechanisms of estrogens’ inhibitory effects on HCC development, RNA sequencing was used to generate comprehensive global transcriptome profiles of the human HCC-derived HepG2 cell line following treatment of vehicle (control), estradiol (E2), estrogen receptor alpha- (ERα-) specific agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT), or ERβ-specific agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) using a small set of cells. Gene ontology (GO) analysis identified increased expression of genes involved in the biological process (BP) of response to different stimuli and metabolic processes by E2 and ER agonists, which enhanced molecular function (MF) in various enzyme activities and chemical bindings. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional pathway analysis indicated enhanced pathways associated with carbohydrate metabolism, complement and coagulation cascades, and HIF-1 signaling pathway by E2 and ER agonists. GO analysis also identified decreased expression of genes by E2, PPT, and DPN involved in BP related to the cell cycle and cell division, which reduced MF in activity of multiple enzymes and microtubule activity. KEGG analysis indicated that E2, PPT, and DPN suppressed pathways associated with the cell cycle; E2 and PPT suppressed pathways associated with chemical carcinogenesis and drug metabolism, and DPN suppressed DNA replication, recombination, and repair. Collectively, these differentially expressed genes across HepG2 cell transcriptome involving cellular and metabolic processes by E2 and ER agonists provided mechanistic insight into protective effects of estrogens in HCC development.

scholarly journals MSTN mutant promoted bovine muscle satellite cell proliferation by regulating the binding of SMAD2/SMAD3 with CDKN1C

2021 ◽  
Author(s):  
Li Gao ◽  
Miao-Miao Yang ◽  
Ming-Juan Gu ◽  
Yun-Peng Liu ◽  
Cai-Hong Bu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Chromatin Immunoprecipitation ◽  
Muscle Development ◽  
Chip Assay ◽  
Rna Seq ◽  
Wild Type ◽  
Muscle Satellite Cell ◽  
Bovine Muscle ◽  
Expression Of Genes

Abstract Background: Myostatin (MSTN), also known as growth/differentiation factor 8, mostly expressed in skeletal muscle and plays negative roles in regulation of muscle development. Previous studies had proved that MSTN have important effect on cell proliferation. Therefore we aimed to investigate the mechanism of MSTN in regulating the proliferation of bovine muscle satellite cells (MSCs).Methods: Bovine MSCs of MSTN mutant (MT) and wild type (WT) were obtained, we detected the cell proliferation and cell cycle by EdU proliferation assay and Flow cytometry. Then we detected the expression of genes associated with cell cycle by Real-time PCR and Western blotting . RNA-seq and Chromatin immunoprecipitation (ChIP)assay were performed to research the mechanism of MSTN in regulating the cell proliferation. Results: In this study, we found that MSTN mutant promoted the proliferation of MSCs. The expression of CyclinA, CyclinD and CyclinE were all increased after MSTN mutant, while the expression of CDKN1C (P57), CDKN2A, CDKN2C and CDKN2D were down-regulated, which were consistent with the promotion of cell proliferation. Among these genes, CDKN1C(P57) down-regulated most significantly. RNA-seq results showed that MSTN mutant affected the SMAD binding, so we performed ChIP-qPCR and demonstrated that the SMAD2/SMAD3 transcription factor combined with the promoter of CDKN1C thus to increase the expression of CDKN1C, this demonstrating that MSTN regulated the expression of CDKN1C through SMAD2/SMAD3 complex. Finally, overexpression of SMAD3 in wild type cells increased the expression of CDKN1C, further suggested that SMAD3 regulated the expression of CDKN1C. Conclusion: MSTN mutant down-regulated the expression of SMAD2/SMAD3, then reduced the promotion of SMAD2/SMAD3 to the expression of CDKN1C, thus to inhibit the expression of CDKN1C, then promoting the cell cycle.

scholarly journals AXIN2 reduces the survival of porcine induced pluripotent stem cells (piPSCs)

2021 ◽  
Author(s):  
rui zhang ◽  
Shuai Yu ◽  
Qiaoyan Shen ◽  
Wenxu Zhao ◽  
Juqing Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Pluripotent Stem Cells ◽  
Culture Medium ◽  
Wnt Signaling Pathway ◽  
Rna Seq ◽  
Expression Of Genes ◽  
Induced Pluripotent ◽  
Effect Of Inhibitors

Abstract BackgroundThe establishment of porcine pluripotent stem cells (piPSCs) is still a critical topic and challenging issue. However, all piPSCs are extremely sensitive to changes of the culture conditions.In addition, the side effect of inhibitors in culture medium confine the pluripotency and practicability. This study aimed to investigate the roles of AXIN in piPSCs and further explore the mechanism. Here, porcine AXIN1 gene and AXIN2 were knockdown, cloned, and overexpressed in piPSCs. Digital RNA-seq was performed to explore the mechanism of cell proliferation and anti-apoptosis. ResultsHere, we found (1): overexpression of the porcine AXIN2 gene significantly reduce the survivability of piPSCs, meanwhile wreck the pluripotency of piPSCs; (2): The Digital RNA-seq analysis reveals that AXIN2, as a negative effector of the WNT signaling pathway, whom after knockdown enhances the expression of genes involved in cell cycle such as CCND1, and reduced the expression of genes related to cell differentiation, cell death, and cell apoptosis. ConclusionAXIN2 could reduce the pluripotency and survival of piPSCs and also provided a potential to simplify the cultrue medium.

Biological Analysis and Prognostic Significance of Proliferative Cellular Compartment in Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 667-667 ◽  
Author(s):  
Pau Abrisqueta ◽  
Neus Villamor ◽  
Ana Muntañola ◽  
Carles Codony ◽  
Mireia Camós ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Doubling Time ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Time To Progression ◽  
Ki67 Expression ◽  
Paired Samples ◽  
Expression Of Genes

Abstract Abstract 667 Historically CLL has been considered a non-proliferative disease characterized by accumulation of leukemic cells. However, recent clinical and biological observations are questioning this concept. From the clinical standpoint, although some patients have lymphocyte counts stable during the course of the disease, others exhibit a short lymphocyte doubling time, suggesting the existence of a significant cell proliferation. Some specific anatomic locations (bone marrow (BM) and lymph nodes) seem to be more prone to proliferation than peripheral blood (PB). The amount of cell proliferation and its prognostic significance has not been properly analyzed. Against this background, gene expression profiling of proliferation genes and the amount of cell proliferation in different tissue compartments (BM and PB) were examined in patients with CLL. In isolated CD19/CD5+ tumoral cells from 20 paired PB and BM samples, expression of genes (n=93) involved in the initiation and development of the cell cycle was analyzed by low-density TaqMan® arrays. The amount of proliferative (Ki67 positive) CLL cells was measured by flow cytometry in 50 paired samples. In addition, coexpression of molecules associated with cellular activation (CD38, CD71, CD69), adhesion (CD49d), chemokine receptors (CXCR4, CXCR3, CCR7), interaction between T and B cells (CD86), signaling (ZAP-70), and Toll-like receptors (TLR9) was compared between Ki67+ and Ki67- CLL subpopulations. Finally, the degree of proliferation was correlated with the main clinical and biological characteristics. As assessed by gene expression profile, the great majority of genes involved in the initiation and development of cell cycle were more expressed in BM than in PB. Of note, Ki67+ CLL cells were significantly higher in BM than in PB (mean: 1.13% vs 0.88%; p= 0.004). This difference on Ki67+ expression between BM and PB was particularly significant (mean: 1.6% vs 1.1%; p=0.01) in patients who progressed of their disease at any particularly time (n=20), whereas it was not observed in patients with stable disease. Proliferating (Ki67+) CLL cells had significantly increased expression of ZAP-70 (mean fluorescence intensity (MFI): 162 vs 94, p<0.001), CD38 (MFI: 75 vs 27, p<0.001), CD86 (MFI: 31 vs 11, p=0.002), CD71 (MFI: 73 vs 24, p<0.001), and TLR9 (MFI: 49 vs 25, p<0.001) in comparison to non-proliferating Ki67- cells; CXCR4 was significantly decreased in proliferating cells (MFI: 212 vs 340, p=0.006). No differences were observed in CD49d, CD69, CCR7, and CXCR3 expression between Ki67+ and Ki67- CLL cells. When Ki67 expression was analyzed at diagnosis (n=41 paired samples, median follow-up of 4.2 years), patients with Ki67+ CLL cells ≥ 1% in BM had a shorter time to progression than those with Ki67 <1% (progression at 4 years: 47% vs 12%, respectively; p=0.008) (figure). In addition, patients with lymphocyte doubling time < 12 months, ZAP-70 expression ≥ 20%, or CD38 expression ≥ 30%, but not with increased CD49d expression, exhibit a higher percentage of Ki67+ CLL cells in both BM and PB (Table). In conclusion, in CLL expression of genes related to proliferation was significantly increased in BM compared to PB. Moreover, the number of proliferating CLL cells was also increased in BM, particularly in those patients with an aggressive disease, and presented different immunophenotype characteristics in comparison to non-proliferating CLL cells. Finally, the amount of Ki67+ CLL cells correlated with a shorter time to progression. These results challenge the concept of CLL as disease more accumulative than proliferative. These new insights on the proliferation pathways in CLL not only may provide a better understanding of the pathogenesis of this disease, but also would be of prognostic relevance and can support the use of new treatments aimed at inhibiting proliferation in CLL. Lymphocyte doubling timeZAP-70CD38CD49d<12 months (n=10)>12 months (n=37)≥20% (n=15)<20% (n=35)≥30% (n=19)<30% (n=31)≥30% (n=17)<30% (n=32)Mean% Ki67+ CLL cells in PB1.20.7P=0.021.40.6P<0.0011.10.7P=0.0151.10.8P=0.08Mean% Ki67+ CLL cells in BM1.60.8P=0.03220.8P=0.0011.31P=0.191.50.9P=0.053 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Raltitrexed Inhibits HepG2 Cell Proliferation via G0/G1 Cell Cycle Arrest

2016 ◽  
Vol 23 (5) ◽  
pp. 237-248 ◽  
Author(s):  
Hongwei Zhao ◽  
Yubao Zhang ◽  
Jianmin Sun ◽  
Chao Zhan ◽  
Liang Zhao
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Hepg2 Cell ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

scholarly journals Hcm1 integrates signals from Cdk1 and calcineurin to control cell proliferation

2015 ◽  
Vol 26 (20) ◽  
pp. 3570-3577 ◽  
Author(s):  
Heather E. Arsenault ◽  
Jagoree Roy ◽  
Claudine E. Mapa ◽  
Martha S. Cyert ◽  
Jennifer A. Benanti
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Chromosome Segregation ◽  
Genome Stability ◽  
Control Cell ◽  
Cell Cycle Regulators ◽  
Cyclin Dependent Kinase ◽  
Expression Of Genes ◽  
Response To Stress

Cyclin-dependent kinase (Cdk1) orchestrates progression through the cell cycle by coordinating the activities of cell-cycle regulators. Although phosphatases that oppose Cdk1 are likely to be necessary to establish dynamic phosphorylation, specific phosphatases that target most Cdk1 substrates have not been identified. In budding yeast, the transcription factor Hcm1 activates expression of genes that regulate chromosome segregation and is critical for maintaining genome stability. Previously we found that Hcm1 activity and degradation are stimulated by Cdk1 phosphorylation of distinct clusters of sites. Here we show that, upon exposure to environmental stress, the phosphatase calcineurin inhibits Hcm1 by specifically removing activating phosphorylations and that this regulation is important for cells to delay proliferation when they encounter stress. Our work identifies a mechanism by which proliferative signals from Cdk1 are removed in response to stress and suggests that Hcm1 functions as a rheostat that integrates stimulatory and inhibitory signals to control cell proliferation.

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