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 Effects of Aspergillus fumigatus Conidia on Apoptosis and Proliferation in an In Vitro Model of the Lung Microenvironment

2021 ◽  
Vol 9 (7) ◽  
pp. 1435
Author(s):  
Hisako Kushima ◽  
Toshiyuki Tsunoda ◽  
Taichi Matsumoto ◽  
Yoshiaki Kinoshita ◽  
Koichi Izumikawa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Aspergillus Fumigatus ◽  
Rna Sequencing ◽  
A549 Cells ◽  
Western Blots ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Nih 3T3

Background/Aim: Aspergillus is often detected in respiratory samples from patients with chronic respiratory diseases, including pulmonary fibrosis, suggesting that it can easily colonize the airways. To determine the role of Aspergillus colonization in pulmonary fibrosis, we cultured human lung epithelial A549 cells or murine embryo fibroblast NIH/3T3 cells with Aspergillus conidia in 3D floating culture representing the microenvironment. Materials and Methods: Cells were cultured in two-dimensional (2D) and three-dimensional floating (3DF) culture with heat-inactivated Aspergillus fumigatus (AF) 293 conidia at an effector-to-target cell ratio of 1:10 (early-phase model) and 1:100 (colonization model), and RNA-sequencing and Western blots (WB) were performed. Results: AF293 conidia reduced A549 cell growth in 2D and 3DF cultures and induced apoptosis in A549 spheroids in 3DF culture. RNA-sequencing revealed the increased expression of genes associated with interferon-mediated antiviral responses including MX dymamin-like GTPase 1 (MX1). Interestingly, the decreased expression of genes associated with the cell cycle was observed with a high concentration of AF293 conidia. WB revealed that epithelial-mesenchymal transition was not involved. Notably, AF293 conidia increased NIH/3T3 growth only in 3DF culture without inducing an apoptotic reaction. RNA-sequencing revealed the increased expression of genes associated with interferon signalling, including MX2; however, the decreased expression of genes associated with the cell cycle was not observed. Conclusions: AF affects both apoptosis of epithelial cells and the growth of fibroblasts. A deeper understanding of the detailed mechanisms underlying Aspergillus-mediated signaling pathway in epithelial cells and fibroblasts will help us to understand the lung microenvironment.

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.

Anticancer Effect of Amygdalin (Vitamin B-17) on Hepatocellular Carcinoma Cell Line (HepG2) in the Presence and Absence of Zinc

2020 ◽  
Vol 20 (4) ◽  
pp. 486-494
Author(s):  
Mohamed A. El-Desouky ◽  
Abdelgawad A. Fahmi ◽  
Ibrahim Y. Abdelkader ◽  
Karima M. Nasraldin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cytochrome C ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Hepg2 Cell ◽  
Caspase 3 ◽  
Vitamin B ◽  
Cycle Arrest ◽  
Hepg2 Cell Lines

Background: Amygdalin (Vitamin B-17) is a naturally occurring vitamin found in the seeds of the fruits of Prunus Rosacea family including apricot, bitter almond, cherry, and peach. Objective: The purpose of this study was to examine the effect of amygdalin with and without zinc on hepatocellular carcinoma (HepG2) cell line. Methods: MTT assay was used to evaluate the cytotoxicity of amygdalin without zinc, amygdalin + 20μmol zinc, and amygdalin + 800μmol zinc on HepG2 cell lines. The cell cycle distribution assay was determined by flow cytometry. Apoptosis was confirmed by Annexin V-FITC/PI staining assay. Moreover, the pathway of apoptosis was determined by the percentage of change in the mean levels of P53, Bcl2, Bax, cytochrome c, and caspase-3. Results: Amygdalin without zinc showed strong anti-HepG2 activity. Furthermore, HepG2 cell lines treatment with amygdalin + 20μmol zinc and amygdalin + 800μmol zinc showed a highly significant apoptotic effect than the effect of amygdalin without zinc. Amygdalin treatment induced cell cycle arrest at G2/M and increased the levels of P53, Bax, cytochrome c, and caspase-3 significantly, while it decreased the level of anti-apoptotic Bcl2. Conclusion: Amygdalin is a natural anti-cancer agent, which can be used for the treatment of hepatocellular carcinoma. It promotes apoptosis via the intrinsic cell death pathway (the mitochondria-initiated pathway) and cell cycle arrest at G/M. The potency of amygdalin in HepG2 treatment increased significantly by the addition of zinc.

A resveratrol analog, phoyunbene B, induces G2/M cell cycle arrest and apoptosis in HepG2 liver cancer cells

2012 ◽  
Vol 22 (5) ◽  
pp. 2114-2118 ◽  
Author(s):  
Guanghui Wang ◽  
Xiaoyu Guo ◽  
Haifeng Chen ◽  
Ting Lin ◽  
Yang Xu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
M Cell ◽  
Liver Cancer Cells ◽  
Cycle Arrest

Landscape analysis of lncRNAs shows that DDX11-AS1 promotes cell-cycle progression in liver cancer through the PARP1/p53 axis

2021 ◽  
Author(s):  
Mengxiang Xu ◽  
Xinyi Zhao ◽  
Shu Zhao ◽  
Zhongli Yang ◽  
Wenji Yuan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Liver Cancer ◽  
Cell Cycle Progression ◽  
Landscape Analysis ◽  
Cycle Progression

scholarly journals Repression of ESR1 through Actions of Estrogen Receptor Alpha and Sin3A at the Proximal Promoter

2009 ◽  
Vol 29 (18) ◽  
pp. 4949-4958 ◽  
Author(s):  
Stephanie J. Ellison-Zelski ◽  
Natalia M. Solodin ◽  
Elaine T. Alarid
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Transcriptional Repression ◽  
Estrogen Receptor Alpha ◽  
Proximal Promoter ◽  
Receptor Alpha ◽  
Expression Of Genes ◽  
Activation Of Transcription

ABSTRACT Gene expression results from the coordinated actions of transcription factor proteins and coregulators. Estrogen receptor alpha (ERα) is a ligand-activated transcription factor that can both activate and repress the expression of genes. Activation of transcription by estrogen-bound ERα has been studied in detail, as has antagonist-induced repression, such as that which occurs by tamoxifen. How estrogen-bound ERα represses gene transcription remains unclear. In this report, we identify a new mechanism of estrogen-induced transcriptional repression by using the ERα gene, ESR1. Upon estrogen treatment, ERα is recruited to two sites on ESR1, one distal (ENH1) and the other at the proximal (A) promoter. Coactivator proteins, namely, p300 and AIB1, are found at both ERα-binding sites. However, recruitment of the Sin3A repressor, loss of RNA polymerase II, and changes in histone modifications occur only at the A promoter. Reduction of Sin3A expression by RNA interference specifically inhibits estrogen-induced repression of ESR1. Furthermore, an estrogen-responsive interaction between Sin3A and ERα is identified. These data support a model of repression wherein actions of ERα and Sin3A at the proximal promoter can overcome activating signals at distal or proximal sites and ultimately decrease gene expression.

EPA and DHA confer protection against DON-induced endoplasmic reticulum stress and iron imbalance in IPEC-1 cells

2021 ◽  
pp. 1-29
Author(s):  
Jia Lin ◽  
Feifei Huang ◽  
Tianzeng Liang ◽  
Qin Qin ◽  
Qiao Xu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Rna Sequencing ◽  
Cell Injury ◽  
Cell Damage ◽  
Binding Protein ◽  
Sequencing Analysis ◽  
Epa And Dha ◽  
Expression Of Genes ◽  
Transferrin Receptor 1

Abstract This study assessed the molecular mechanism of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) protection against IPEC-1 cell damage induced by deoxynivalenol (DON). The cells were divided into six groups, including the CON group, the EPA group, the DHA group, the DON group, the EPA+DON group, and the DHA+DON group. RNA sequencing was used to investigate the potential mechanism, and qRT-PCR was employed to verify the expression of selected genes. Changes in ultrastructure were used to estimate pathological changes and endoplasmic reticulum (ER) injury in IPEC-1 cells. Transferrin receptor 1 (TFR1) was tested by ELISA. Fe2+ and malondialdehyde (MDA) contents were estimated by spectrophotometry, and reactive oxygen species (ROS) was assayed by fluorospectrophotometry. RNA sequencing analysis showed that EPA and DHA had a significant effect on the expression of genes involved in ER stress and iron balance during DON-induced cell injury. The results showed that DON increased ER damage, the content of MDA and ROS, the ratio of X-box binding protein 1s (XBP-1s)/X-box binding protein 1u (XBP-1u), the concentration of Fe2+, and the activity of TFR1. However, the results also showed that EPA and DHA decreased the ratio of XBP-1s/XBP-1u to relieve DON-induced ER damage of IPEC-1 cells. Moreover, EPA and DHA (especially DHA) reversed the factors related to iron balance. It can be concluded that EPA and DHA reversed IPEC-1 cell damage induced by DON. DHA has the potential to protect IPEC-1 cells from DON-induced iron imbalance by inhibiting ER stress.

scholarly journals Regulation of Steroid Hormone Receptors and Coregulators during the Cell Cycle Highlights Potential Novel Function in Addition to Roles as Transcription Factors

2016 ◽  
Vol 14 (1) ◽  
pp. nrs.14001 ◽  
Author(s):  
Yingfeng Zheng ◽  
Leigh C. Murphy
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Transcriptional Activity ◽  
Hormone Receptors ◽  
Steroid Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Cycle Progression ◽  
Expression Of Genes ◽  
Cycle Regulation

Cell cycle progression is tightly controlled by several kinase families including Cyclin-Dependent Kinases, Polo-Like Kinases, and Aurora Kinases. A large amount of data show that steroid hormone receptors and various components of the cell cycle, including cell cycle regulated kinases, interact, and this often results in altered transcriptional activity of the receptor. Furthermore, steroid hormones, through their receptors, can also regulate the transcriptional expression of genes that are required for cell cycle regulation. However, emerging data suggest that steroid hormone receptors may have roles in cell cycle progression independent of their transcriptional activity. The following is a review of how steroid receptors and their coregulators can regulate or be regulated by the cell cycle machinery, with a particular focus on roles independent of transcription in G2/M.

Effect of gestational protein deficiency and excess on hepatic expression of genes related to cell cycle and proliferation in offspring from late gestation to finishing phase in pig

2012 ◽  
Vol 39 (6) ◽  
pp. 7095-7104 ◽  
Author(s):  
Simone Altmann ◽  
Eduard Murani ◽  
Cornelia C. Metges ◽  
Manfred Schwerin ◽  
Klaus Wimmers ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Deficiency ◽  
Late Gestation ◽  
Hepatic Expression ◽  
Expression Of Genes
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