scholarly journals CCNE1 and E2F1 Partially Suppress G1 Phase Arrest Caused by Spliceostatin A Treatment

2021 ◽  
Vol 22 (21) ◽  
pp. 11623
Author(s):  
Kei Kikuchi ◽  
Daisuke Kaida
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
G1 Phase ◽  
Cell Cycle Regulators ◽  
Protein Levels ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Spliceostatin A

The potent splicing inhibitor spliceostatin A (SSA) inhibits cell cycle progression at the G1 and G2/M phases. We previously reported that upregulation of the p27 cyclin-dependent kinase inhibitor encoded by CDKN1B and its C-terminal truncated form, namely p27*, which is translated from CDKN1B pre-mRNA, is one of the causes of G1 phase arrest caused by SSA treatment. However, the detailed molecular mechanism underlying G1 phase arrest caused by SSA treatment remains to be elucidated. In this study, we found that SSA treatment caused the downregulation of cell cycle regulators, including CCNE1, CCNE2, and E2F1, at both the mRNA and protein levels. We also found that transcription elongation of the genes was deficient in SSA-treated cells. The overexpression of CCNE1 and E2F1 in combination with CDKN1B knockout partially suppressed G1 phase arrest caused by SSA treatment. These results suggest that the downregulation of CCNE1 and E2F1 contribute to the G1 phase arrest induced by SSA treatment, although they do not exclude the involvement of other factors in SSA-induced G1 phase arrest.

scholarly journals Invadopodia degrade ECM in the G1 phase of the cell cycle

2018 ◽  
Author(s):  
Battuya Bayarmagnai ◽  
Louisiane Perrin ◽  
Kamyar Esmaeili Pourfarhangi ◽  
Bojana Gligorijevic
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
G1 Phase ◽  
Specific Cell ◽  
Cell Cycle Regulators ◽  
Cycle Progression ◽  
Protein Levels ◽  
Fluorescent Markers ◽  
Ecm Degradation

AbstractInvadopodia are cancer cell protrusions rich in structural proteins (e.g. Tks5, cortactin) and proteases (e.g. MT1-MMP) and are responsible for degradation of the extracellular matrix (ECM). Tumor cell invasion and metastasis require cancer cells to be both proliferative and invasive, i.e. migrate through the tissue and assemble invadopodia. While several studies addressed how cell motility parameters change throughout the cell cycle, the relationship between invadopodia and cell cycle progression has not been elucidated. In this study, using invadopodia- and cell cycle- fluorescent markers, we show in 2D and 3D cell cultures, as well as in vivo, that breast carcinoma cells assemble invadopodia and invade into the surrounding ECM preferentially during the G1 phase of the cell cycle. Cells synchronized in the G0/G1 phase of the cell cycle degrade at significantly higher levels during the first 20 hours post-synchronization release. Consistent with this, mRNA and protein levels of the invadopodia key components, cortactin and MT1-MMP, peak at 14 hours post-release. Cell cycle progression is faster in cells in which invadopodia are abolished (by Tks5 knockdown), evidenced by earlier induction of cyclins A and B. A close look at the regulators of G1 revealed that the overexpression of p27kip1, but not p21cip1, causes faster turnover of invadopodia and increased ECM degradation. Furthermore, both endogenous and over-expressed p27kip1 localizes to the sites of invadopodia assembly. Taken together, these findings suggest that invadopodia function is tightly linked to cell cycle progression and is controlled by specific cell cycle regulators. Our results caution that this coordination between invasion and cell cycle must be considered when designing effective chemotherapies.

Long Noncoding RNA GAS5 Targeting miR-221-3p/Cyclin-Dependent Kinase Inhibitor 2B Axis Regulates Follicular Thyroid Carcinoma Cell Cycle and Proliferation

Pathobiology ◽  
2021 ◽  
pp. 1-12
Author(s):  
Yuan Liu ◽  
Yi-Fang Li ◽  
Jia Liu ◽  
Zhi-Gang Deng ◽  
Li Zeng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Thyroid Carcinoma ◽  
Noncoding Rna ◽  
Kinase Inhibitor ◽  
Follicular Thyroid Carcinoma ◽  
Cyclin Dependent Kinase ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phase Arrest ◽  
G1 Phase Arrest

<b><i>Introduction:</i></b> Follicular thyroid carcinoma (FTC) is more aggressive than the most common papillary thyroid carcinoma (PTC). However, the current research on FTC is less than PTC. Here, we investigated the effects of long noncoding RNA (lncRNA) GAS5 and miR-221-3p in FTC. <b><i>Methods:</i></b> Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect GAS5 and miR-221-3p expression in the FTC tissues and cells. Cell proliferation was assessed by CCK8 and EdU assays. Flow cytometry was performed to determine the cell cycle. The dual-luciferase reporter assay was employed to validate the binding relationship of GAS5/miR-221-3p and miR-221-3p/cyclin-dependent kinase inhibitor 2B (CDKN2B). Western blot was conducted to measure the protein level of CDKN2B. <b><i>Results:</i></b> Our results displayed that GAS5 was downregulated, while miR-221-3p was upregulated in FTC tissues and cells. What’s more, overexpression of GAS5 or miR-221-3p inhibition induced G0/G1 phase arrest and inhibited cell proliferation of FTC cells. GAS5 acted as a sponge of miR-221-3p, and CDKN2B was a target gene of miR-221-3p. Additionally, GAS5 inhibited cell cycle and proliferation of FTC cells via reducing miR-221-3p expression to enhance CDKN2B expression. <b><i>Conclusion:</i></b> GAS5 induced G0/G1 phase arrest and inhibited cell proliferation via targeting miR-221-3p/CDKN2B axis in FTC. Thus, GAS5 may be a potential therapeutic target for the treatment of FTC.

scholarly journals Overexpression of USF Increases TGF-β1 Protein Levels, But G1 Phase Arrest was not Induced in FRTL-5 Cells

2008 ◽  
Vol 23 (5) ◽  
pp. 870 ◽  
Author(s):  
Keun-Sook Kim ◽  
Hye Seung Jung ◽  
Yun Jae Chung ◽  
Tae Sik Jung ◽  
Hye Won Jang ◽  
...  
Keyword(s):  
G1 Phase ◽  
Protein Levels ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Tgf Β1

scholarly journals Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1498-1505 ◽  
Author(s):  
Jürgen den Hollander ◽  
Sara Rimpi ◽  
Joanne R. Doherty ◽  
Martina Rudelius ◽  
Andreas Buck ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Cell Cycle Regulators ◽  
Aurora Kinase Inhibitor ◽  
Aurora Kinases ◽  
Protein Levels ◽  
Malignant State ◽  
E Boxes

Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly. Blocking Aurka/b kinase activity with a selective Aurora kinase inhibitor triggers transient mitotic arrest, polyploidization, and apoptosis of Myc-induced lymphomas. These phenotypes are selectively bypassed by a kinase inhibitor-resistant Aurkb mutant, demonstrating that Aurkb is the primary therapeutic target in the context of Myc. Importantly, apoptosis provoked by Aurk inhibition was p53 independent, suggesting that Aurka/Aurkb inhibitors will show efficacy in treating primary or relapsed malignancies having Myc involvement and/or loss of p53 function.

Paradoxical accumulation of the cyclin-dependent kinase inhibitor p27kip1 during the cAMP-dependent mitogenic stimulation of thyroid epithelial cells

1996 ◽  
Vol 109 (7) ◽  
pp. 1759-1764
Author(s):  
F. Depoortere ◽  
J.E. Dumont ◽  
P.P. Roger
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Concomitant Administration ◽  
Growth Stimulation ◽  
Positive Control ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Enhanced Expression

In different systems, cAMP either blocks or promotes cell cycle progression in mid to late G1 phase. Dog thyroid epithelial cells in primary culture constitute a model of positive control of DNA synthesis initiation and G0-S pre-replicative phase progression by cyclic AMP (cAMP) as a second messenger for thyrotropin (TSH). We report here that TSH markedly increases the expression of p27kip1, the inhibitor of the cell cycle and cyclin-dependent kinases. This effect was prevented by the concomitant administration of the cAMP-independent mitogens, epidermal growth factor (EGF)+serum. EGF+serum also slightly inhibited the weak basal accumulation of p27kip1. Nevertheless, in the case of stimulation by TSH alone, the cAMP-dependent cell cycle progression was fully compatible with the enhanced expression of p27kip1. This observation is paradoxical since a decrease of p27kip1 is generally associated with growth stimulation in other systems, and since a similar cAMP-dependent increase of p27kip1 in macrophages has been found responsible for mid-G1 cell cycle arrest. The opposite regulation of p27kip1 in response to TSH or EGF+serum in dog thyroid epithelial cells suggests a major difference at mid to late G1 stages between cAMP-dependent and cAMP-independent mitogenic pathways.

scholarly journals MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression

2008 ◽  
Vol 28 (7) ◽  
pp. 2167-2174 ◽  
Author(s):  
Irena Ivanovska ◽  
Alexey S. Ball ◽  
Robert L. Diaz ◽  
Jill F. Magnus ◽  
Miho Kibukawa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Phenotype Microarray ◽  
Loss Of Function ◽  
Cycle Progression ◽  
Multiple Tumor ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Expression Of Genes ◽  
Tumor Types

ABSTRACT microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions.

scholarly journals Hepatitis B virus induces G1 phase arrest by regulating cell cycle genes in HepG2.2.15 cells

2011 ◽  
Vol 8 (1) ◽  
pp. 231 ◽  
Author(s):  
Tianzhen Wang ◽  
Ran Zhao ◽  
Yiqi Wu ◽  
Dan Kong ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
G1 Phase ◽  
Cell Cycle Genes ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
B Virus

scholarly journals Transcriptional Downregulation of p27KIP1 through Regulation of E2F Function during LMP1-Mediated Transformation

2009 ◽  
Vol 83 (24) ◽  
pp. 12671-12679 ◽  
Author(s):  
David N. Everly ◽  
Bernardo A. Mainou ◽  
Nancy Raab-Traub
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Inhibitor ◽  
Cyclin Dependent Kinase ◽  
Mobility Shift ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Phenotypic Transformation ◽  
Electrophoretic Mobility Shift Assays ◽  
Posttranscriptional Level

ABSTRACT LMP1 induces the phenotypic transformation of fibroblasts and affects regulators of the cell cycle during this process. LMP1 decreases expression of the cyclin-dependent kinase inhibitor p27 and increases the levels and phosphorylation of cyclin-dependent kinase 2 and the retinoblastoma protein. In the present study, the effects of LMP1 on cell cycle progression and the mechanism of p27 downregulation by LMP1 were determined. Although p27 is frequently regulated at the posttranscriptional level during cell cycle progression and in cancer, LMP1 did not decrease ectopically expressed p27. However, LMP1 did decrease p27 RNA levels and inhibited the activity of p27 promoter reporters. The LMP1-regulated promoter element was mapped to a region containing two E2F sites. Electrophoretic mobility shift assays determined that the regulated cis element bound an inhibitory E2F complex containing E2F4 and p130. These findings indicate that LMP1 decreases p27 transcription through effects on E2F family transcription factors. This property likely contributes to the ability of LMP1 to stimulate cell cycle progression.

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