scholarly journals ESRP1 Induces Cervical Cancer Cell G1-Phase Arrest Via Regulating Cyclin A2 mRNA Stability

2019 ◽  
Vol 20 (15) ◽  
pp. 3705 ◽  
Author(s):  
Zhi-Hong Chen ◽  
Ya-Jie Jing ◽  
Jian-Bo Yu ◽  
Zai-Shu Jin ◽  
Zhu Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cervical Carcinoma ◽  
Carcinoma Cell ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Cyclin A2 ◽  
The Stability

Accumulating evidence indicates that epithelial splicing regulatory protein 1 (ESRP1) can inhibit the epithelial-to-mesenchymal transition (EMT), thus playing a central role in regulating the metastatic progression of tumors. However, it is still not clear whether ESRP1 directly influences the cell cycle, or what the possible underlying molecular mechanisms are. In this study, we showed that ESRP1 protein levels were significantly correlated with the Ki-67 proliferative index (r = −0.521; p < 0.01), and that ESRP1 overexpression can significantly inhibit cervical carcinoma cell proliferation and induced G1-phase arrest by downregulating cyclin A2 expression. Importantly, ESRP1 can bind to GGUGGU sequence in the 3′UTR of the cyclin A2 mRNA, and ESRP1 overexpression significantly decreases the stability of the cyclin A2 mRNA. In addition, our experimental results confirm that ESRP1 overexpression results in enhanced CDC20 expression, which is known to be responsible for cyclin A2 degradation. This study provides the first evidence that ESRP1 overexpression induces G1-phase cell cycle arrest via reducing the stability of the cyclin A2 mRNA, and inhibits cervical carcinoma cell proliferation. The findings suggest that the ESRP1/cyclin A2 regulatory axis may be essential as a regulator of cell proliferation, and may thus represent an attractive target for cervical cancer prevention and treatment.

scholarly journals Overexpression of cell cycle regulator CDCA3 promotes oral cancer progression by enhancing cell proliferation with prevention of G1 phase arrest

BMC Cancer ◽  
2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Fumihiko Uchida ◽  
Katsuhiro Uzawa ◽  
Atsushi Kasamatsu ◽  
Hiroaki Takatori ◽  
Yosuke Sakamoto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Oral Cancer ◽  
Cancer Progression ◽  
G1 Phase ◽  
Phase Arrest ◽  
Cell Cycle Regulator ◽  
G1 Phase Arrest

scholarly journals Cell Cycle Regulation of Hippocampal Progenitor Cells in Experimental Models of Depression and after Treatment with Fluoxetine

2021 ◽  
Vol 22 (21) ◽  
pp. 11798
Author(s):  
Patrícia Patrício ◽  
António Mateus-Pinheiro ◽  
Ana Rita Machado-Santos ◽  
Nuno Dinis Alves ◽  
Joana Sofia Correia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Progenitor Cells ◽  
Antidepressant Treatment ◽  
G1 Phase ◽  
Phase Arrest ◽  
Hippocampal Cell ◽  
G1 Phase Arrest

Changes in adult hippocampal cell proliferation and genesis have been largely implicated in depression and antidepressant action, though surprisingly, the underlying cell cycle mechanisms are largely undisclosed. Using both an in vivo unpredictable chronic mild stress (uCMS) rat model of depression and in vitro rat hippocampal-derived neurosphere culture approaches, we aimed to unravel the cell cycle mechanisms regulating hippocampal cell proliferation and genesis in depression and after antidepressant treatment. We show that the hippocampal dentate gyrus (hDG) of uCMS animals have less proliferating cells and a decreased proportion of cells in the G2/M phase, suggesting a G1 phase arrest; this is accompanied by decreased levels of cyclin D1, E, and A expression. Chronic fluoxetine treatment reversed the G1 phase arrest and promoted an up-regulation of cyclin E. In vitro, dexamethasone (DEX) decreased cell proliferation, whereas the administration of serotonin (5-HT) reversed it. DEX also induced a G1-phase arrest and decreased cyclin D1 and D2 expression levels while increasing p27. Additionally, 5-HT treatment could partly reverse the G1-phase arrest and restored cyclin D1 expression. We suggest that the anti-proliferative actions of chronic stress in the hDG result from a glucocorticoid-mediated G1-phase arrest in the progenitor cells that is partly mediated by decreased cyclin D1 expression which may be overcome by antidepressant treatment.

scholarly journals Cell Proliferation and Motility Are Inhibited by G1 Phase Arrest in 15-kDa Selenoprotein-Deficient Chang Liver Cells

2015 ◽  
Vol 38 (5) ◽  
pp. 457-465 ◽  
Author(s):  
Jeyoung Bang ◽  
Jang Hoe Huh ◽  
Ji-Woon Na ◽  
Qiao Lu ◽  
Bradley A. Carlson ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cells ◽  
G1 Phase ◽  
Phase Arrest ◽  
G1 Phase Arrest ◽  
Chang Liver

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 Icariin affects cell cycle progression and proliferation of human retinal pigment epithelial cells via enhancing expression of H19

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8830
Author(s):  
Yibing Zhang ◽  
Min Li ◽  
Xue Han
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Retinal Pigment Epithelial ◽  
Retinal Pigment ◽  
Inhibitory Effects ◽  
Cycle Progression ◽  
Rpe Cells ◽  
Phase Arrest ◽  
G1 Phase Arrest

Background Aberrant proliferation of retinal pigment epithelial (RPE) cells under pathologic condition results in the occurrence of proliferative vitreoretinopathy (PVR). Icariin (ICA)-a flavonol glucoside-has been shown to inhibit proliferation of many cell types, but the effect on RPE cells is unknown. This study aimed to clarify the inhibitory effects of ICA on RPE cells against platelet-derived growth factor (PDGF)-BB-induced cell proliferation, and discuss the regulatory function of H19 in RPE cells. Methods MTS assay was conducted to determine the effects of ICA on cell proliferation. Flow cytometry analysis was performed to detect cell cycle progression. Quantitative real-time PCR and western blot assay were used to measure the expression patterns of genes in RPE cells. Results ICA significantly suppressed PDGF-BB-stimulated RPE cell proliferation in a concentration-dependent manner. Moreover, since administration of ICA induced cell cycle G0/G1 phase arrest, the anti-proliferative activity of ICA may be due to G0/G1 phase arrest in RPE cells. At molecular levels, cell cycle regulators cyclin D1, CDK4, CDK6, p21 and p53 were modulated in response to treatment with ICA. Most importantly, H19 was positively regulated by ICA and H19 depletion could reverse the inhibitory effects of ICA on cell cycle progression and proliferation in PDGF-BB-stimulated RPE cells. Further mechanical explorations showed that H19 knockdown resulted in alternative expressions levels of cyclin D1, CDK4, CDK6, p21 and p53 under ICA treatment. Conclusions Our findings revealed that ICA was an effective inhibitor of PDGF-BB-induced RPE cell proliferation through affecting the expression levels of cell cycle-associated factors, and highlighted the potential application of ICA in PVR therapy. H19 was described as a target regulatory gene of ICA whose disruption may contribute to excessive proliferation of RPE cells, suggesting that modulation of H19 expression may be a novel therapeutic approach to treat PVR.

scholarly journals Glucocappasalin Induces G2/M-Phase Arrest, Apoptosis, and Autophagy Pathways by Targeting CDK1 and PLK1 in Cervical Carcinoma Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Guangya Xu ◽  
Xueling Yan ◽  
Zhongjia Hu ◽  
Lulu Zheng ◽  
Ke Ding ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Carcinoma Cells ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
M Phase

Glucocappasalin (GCP), a natural product derived from the seeds of Descurainia sophia (L.) Webb. ex Prantl, exhibits potential antitumor activity in HeLa cervical carcinoma cells. In this study, we investigated the anti-cervical cancer property of GCP through the induction of cell cycle arrest, apoptosis, and autophagy in vitro and in vivo, and elucidated the underlying molecular mechanisms. We demonstrated that treatment with GCP inhibited the growth of HeLa, Siha, and Ca Ski cell lines in a dose-dependent manner, with HeLa cells displaying particular sensitivity to the GCP treatment. Subsequently, the expression of cyclin-dependent kinase 1 (CDK1) and polo like kinase 1 (PLK1) were evaluated in HeLa cells using the CDK1 kinase assay kit, the fluorescence polarization assay, real-time quantitative PCR, and western blotting. Our results demonstrate that GCP could be employed to attenuate the expression of CDK1 and PLK1 in a dose- and time-dependent manner. The complementary results obtained by flow cytometry and western blotting allowed us to postulate that GCP may exhibit its antitumor effects by inducing G2/M cell cycle arrest. Moreover, HeLa cells treated with GCP exhibited a loss in mitochondrial membrane potential, together with the activation of caspases 3 and 9, and poly ADP-ribose polymerase (PARP). Additionally, we found that GCP could increase the formation of acidic vesicular organelles (AVOs), as well as the levels of Beclin1, LC3-II, p62, and Atg5 proteins in HeLa cells. Further studies indicated that GCP triggered autophagy via the suppression of the PI3K/AKT/mTOR signaling pathways. The autophagy inhibitor 3-methyladenine (3-MA) was used to determine whether autophagy affects the apoptosis induced by GCP. Interestingly, the inhibition of autophagy attenuated apoptosis. In vivo anti-tumor experiments indicated that GCP (60 mg/kg, i.p.) markedly reduced the growth of HeLa xenografts in nude mice without apparent toxicity. Taken together, we demonstrate that GCP induces cell cycle G2/M-phase arrest, apoptosis, and autophagy by acting on the PI3K/AKT/mTOR signaling pathways in cervical carcinoma cells. Thus, GCP may represent a promising agent in the eradication of cervical cancer.

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 Dimethylfumarate Inhibits Colorectal Carcinoma Cell Proliferation: Evidence for Cell Cycle Arrest, Apoptosis and Autophagy

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1329 ◽  
Author(s):  
Kaluzki ◽  
Hailemariam-Jahn ◽  
Doll ◽  
Kaufmann ◽  
Balermpas ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Proliferation ◽  
Colorectal Carcinoma ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Carcinoma Cell ◽  
Human Colon ◽  
G1 Phase ◽  
Cycle Arrest

Recent studies have proven that Dimethylfumarate (DMF) has a marked anti-proliferative impact on diverse cancer entities e.g., on malignant melanoma. To explore its anti-tumorigenic potential, we examined the effects of DMF on human colon carcinoma cell lines and the underlying mechanisms of action. Human colon cancer cell line HT-29 and human colorectal carcinoma cell line T84 were treated with or without DMF. Effects of DMF on proliferation, cell cycle progression, and apoptosis were analyzed mainly by Bromodeoxyuridine (BrdU)- and Lactatdehydrogenase (LDH)assays, caspase activation, flowcytometry, immunofluorescence, and immunoblotting. In addition, combinational treatments with radiation and chemotherapy were performed. DMF inhibits cell proliferation in both cell lines. It was shown that DMF induces a cell cycle arrest in G0/G1 phase, which is accompanied by upregulation of p21 and downregulation of cyclin D1 and Cyclin dependent kinase (CDK)4. Furthermore, upregulation of autophagy associated proteins suggests that autophagy is involved. In addition, the activation of apoptotic markers provides evidence that apoptosis is involved. Our results show that DMF supports the action of oxaliplatin in a synergetic manner and failed synergy with radiation. We demonstrated that DMF has distinct antitumorigenic, cell dependent effects on colon cancer cells by arresting cell cycle in G0/G1 phase as well as activating both the autophagic and apoptotic pathways and synergizes with chemotherapy.

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