scholarly journals Silencing of TBX20 gene expression in rat myocardial and human embryonic kidney cells leads to cell cycle arrest in G2 phase

2016 ◽  
Vol 14 (4) ◽  
pp. 2904-2914
Author(s):  
Peiyan Liu ◽  
Yueling Sun ◽  
Guangbin Qiu ◽  
Hongkun Jiang ◽  
Guangrong Qiu
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Kidney Cells ◽  
Human Embryonic Kidney ◽  
Human Embryonic Kidney Cells ◽  
Cycle Arrest ◽  
G2 Phase

Wogonoside Exerts Anti-Leukemia of AML Cells Via Restricting Phospholipid Scramblase 1 Gene Expression and Promoting Its Translocation Into Nuclear

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4282-4282
Author(s):  
Yan Chen ◽  
Bao-An Chen ◽  
Qing-long Guo
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Underlying Mechanism ◽  
Phase Cell ◽  
Western Blots ◽  
Phospholipid Scramblase ◽  
Cycle Arrest ◽  
Phospholipid Scramblase 1

Abstract Abstract 4282 Objective: To evaluate the antileukemic effect of wogonoside and reveal the underlying mechanism. Method: In this study trypan blue dye exclusion assay, MTT assay, and soft agar colony formation assay were used to analysis growth inhibition of wogonoside the on AML (acute human promyelocytic) cell lines. Propidium iodide (PI)-staining and cell cycle-regulatory proteins detecting by western blots were applied to exam whether wogonoside could induce cell cycle arrest. Then a series of experiment were used to assess the ability of wogonoside to overcome the AML associated differentiation block, by using Giemsa staining, Nitroblue tetrazolium (NBT) reduction assay, and cell-surface differentiation antigens expression analysis. Real time PCR, western blots, cycloheximide inhibition test and RNA interference, nuclear and cytoplasmic fractionation, immunofluorescent staining were used to investigate the underlying mechanism. In this point we mainly focus that wogonoside exerts antileukemic by modulating of PLSCR1 gene expression, as well as influence its subcellular localization to play a role in regulating gene transcription. Result: It was demonstrated that wogonoside have the capacity to decrease the growth of myeloid cell lines by induction of G0/1 phase cell cycle arrest and differentiation. This effect is mediated by the increasing in mRNA and up-regulating protein expression of phospholipids scramblase 1 (PLSCR1). Meanwhile wogonoside promoted PLSCR1 traffic into the nucleus, which let PLSCR1 to play a role in regulating cell cycle and differentiation-related genes transcription including p21, p27, c-myc and IP3R1. Conclusion: Wogonoside induced AML cell lines to undergo differentiation and G1 phase arrest by restricting phospholipid scramblase 1 gene expression and promoting its translocation into nuclear. Disclosures: No relevant conflicts of interest to declare.

The role of HNF4A in GATA4-deficiency phenotypes of hepatocellular carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 284-284
Author(s):  
Yu Bin Tan ◽  
Timothy Shuen ◽  
Han Chong Toh
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Correlation Analysis ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Transgenic Mouse ◽  
Cell Lines ◽  
Downstream Target ◽  
Cycle Arrest

284 Background: Hepatocellular carcinoma (HCC) is the 2nd leading global cause of cancer death. Recently, we have discovered previously undescribed deletion and germline mutation of GATA4 and showed that GATA4 is a key differentiation driver and metabolic regulator in HCC. However, as GATA4 is mostly deleted in HCC, targeting GATA4-downstream molecules is ideal. In this study, proof-of-concept experiments were conducted to show that introduction of HNF4A, which is a GATA4-regulated downstream target, could partially rescue the impaired phenotypes in GATA4-deficient HCC cell line. Methods: Correlation analysis using gene expression microarray of human HCC samples was conducted to identify the genes that are positively correlated with GATA4. A transgenic mouse model with a liver-specific conditional GATA4 knockout was designed to identify liver morphology and gene expression changes which are correlated with the loss of Gata4 in the mouse liver. CRISPR-mediated knockout of GATA4 and lentiviral HNF4A overexpression was carried out in a GATA4-deficient HCC cell lines, PLC/PRF/5 and Hep3B, followed by proliferation, apoptosis, cell cycle and senescence functional assays. Results: Pearson correlation analysis from human HCC samples showed that expression of HNF4A is positively correlated with that of GATA4. Livers from conditional Gata4 knockout mice had lower Hnf4a gene expression when compared to age-matched control mice. Loss of function analysis by CRISPR-mediated GATA4 knockout further showed downregulation of HNF4A in GATA4-deficient PLC/PRF/5 cell line. Lentiviral HNF4A overexpression in PLC/PRF/5 and Hep3B demonstrated reduced proliferation and increased apoptosis while PLC/PRF/5 also showed cell cycle arrest at G2/M phase when compared to control. However, no senescence induction was detected in HNF4A-overexpressing cells. Conclusions: Transgenic mouse data, CRISPR-mediated knockout and analysis of HCC samples showed that HNF4A is a key GATA4-downstream target. HNF4A overexpression decreases proliferation, increases apoptosis and cell cycle arrest in GATA4-deficient HCC cell lines, thus representing a possible therapeutic target for HCC.

scholarly journals Human Immunodeficiency Virus Type 1 Vpr-Dependent Cell Cycle Arrest through a Mitogen-Activated Protein Kinase Signal Transduction Pathway

2005 ◽  
Vol 79 (17) ◽  
pp. 11366-11381 ◽  
Author(s):  
Naoto Yoshizuka ◽  
Yuko Yoshizuka-Chadani ◽  
Vyjayanthi Krishnan ◽  
Steven L. Zeichner
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Human Immunodeficiency Virus ◽  
Cell Cycle Arrest ◽  
Host Cell ◽  
Human Immunodeficiency Virus Type ◽  
Erk Pathway ◽  
Cycle Arrest ◽  
Immunodeficiency Virus

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) Vpr protein has important functions in advancing HIV pathogenesis via several effects on the host cell. Vpr mediates nuclear import of the preintegration complex, induces host cell apoptosis, and inhibits cell cycle progression at G2, which increases HIV gene expression. Some of Vpr's activities have been well described, but some functions, such as cell cycle arrest, are not yet completely characterized, although components of the ATR DNA damage repair pathway and the Cdc25C and Cdc2 cell cycle control mechanisms clearly play important roles. We investigated the mechanisms underlying Vpr-mediated cell cycle arrest by examining global cellular gene expression profiles in cell lines that inducibly express wild-type and mutant Vpr proteins. We found that Vpr expression is associated with the down-regulation of genes in the MEK2-ERK pathway and with decreased phosphorylation of the MEK2 effector protein ERK. Exogenous provision of excess MEK2 reverses the cell cycle arrest associated with Vpr, confirming the involvement of the MEK2-ERK pathway in Vpr-mediated cell cycle arrest. Vpr therefore appears to arrest the cell cycle at G2/M through two different mechanisms, the ATR mechanism and a newly described MEK2 mechanism. This redundancy suggests that Vpr-mediated cell cycle arrest is important for HIV replication and pathogenesis. Our findings additionally reinforce the idea that HIV can optimize the host cell environment for viral replication.

scholarly journals Gene Expression and Cell Cycle Arrest in a Rat Keratinocyte Line Exposed to 56Fe Ions

2007 ◽  
Vol 48 (2) ◽  
pp. 163-170 ◽  
Author(s):  
Feng WU ◽  
Ronghe ZHANG ◽  
Fredric J. BURNS
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cycle Arrest

scholarly journals Invasive Cell Fate Requires G1 Cell-Cycle Arrest and Histone Deacetylase-Mediated Changes in Gene Expression

2015 ◽  
Vol 35 (2) ◽  
pp. 162-174 ◽  
Author(s):  
David Q. Matus ◽  
Lauren L. Lohmer ◽  
Laura C. Kelley ◽  
Adam J. Schindler ◽  
Abraham Q. Kohrman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Fate ◽  
Histone Deacetylase ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest ◽  
Invasive Cell

scholarly journals Coptidis Rhizome inhibits cell growth in HONE-1 cell line by inducing cell cycle arrest and apoptosis

2020 ◽  
Author(s):  
Kim Fey Leu ◽  
Menaga Subramaniam ◽  
Xinghua Wang ◽  
Zao Yang ◽  
Lee Fah Yap ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cytotoxic Effect ◽  
Global Gene Expression ◽  
Chinese Herbal ◽  
Cycle Arrest

Abstract Background Nasopharyngeal carcinoma (NPC) is among the most common head and neck malignancies seen among adults in Malaysia. Therefore, discovery of novel anti-cancer herbal drugs is of importance. In this study, the cytotoxic effect was conducted on a traditional Chinese herbal prescription (Xiao Xian Xiong Decoction (XXXD) that is made up of 3 Chinese herbal medicines, namely Huanglian (Coptidis Rhizome), Banxia (Pinellia Rhizome), Gualuo (Fructus Trichosanthis).Methods The cytotoxic effect of the individual herb and in combination of two and three herbs was studied on 8 nasopharyngeal cancer cell lines. Global gene expression analysis was carried on extracted RNA using nCounter XT Gene Expression Assay.Results TWO-1, TWO-4, HONE-1, SUNE-1, CNE-2, HK-1, CNE-1 and C666-1 treated with Huanglian, the IC50 values obtained were 24.48, 11.77, 4.48, 10.72 6.32, 11.10, 6.77 and 27.30 µg/ml, respectively. For combination of Huanglian and Banxia, the IC50 values obtained were 74.09 µg/ml (TWO-1), 25.80 µg/ml (TWO-4), 38.10 µg/ml (HONE-1), 29.46 µg/ml (SUNE-1), 19.0 µg/ml (CNE-2) and 20.12 µg/ml (HK-1) but did not exert 50% cell killing in CNE-1 and C666-1 cell lines. The IC50 value attained for the combination of Huanglian and Gualuo was 40.70 µg/ml in HONE-1 cell line. The IC50 values obtained for XXXD (triple combination of Huanglian, Banxia and Gualuo)-treated in HONE-1 and CNE-2 cell lines were 88.55 and 92.42 µg/ml, respectively. Out of all these 7 groups of herbal samples, Huanglian showed the highest cytotoxicity against 8 NPC cell lines with the lowest IC50 value of 4.48 µg/ml recorded in HONE-1. Global gene expression showed Huanglian significantly downregulated genes associated with cell cycle arrest and apoptosis, and thus inhibit HONE-1 cell growth.Conclusions This study suggest that Huanglian could be a potent anticancer herb targeting HONE-1 cancer cell line.

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