scholarly journals Orai1 Downregulation Causes Proliferation Reduction and Cell Cycle Arrest via Inactivation of the Ras-NF-κB Signaling Pathway in Osteoblasts

2021 ◽  
Author(s):  
Yunshan Guo ◽  
Dingjun Hao
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Signaling Pathway ◽  
Ras Signaling ◽  
Osteoblast Proliferation ◽  
Cycle Arrest ◽  
Reduce Cell Proliferation ◽  
Interfering Rna

Abstract Background: The purpose of this study was to determine the role of Orai1 in the regulation of the proliferation and cell cycle of osteoblasts. Methods: The expression of Orai1 was inhibited by Orai1 small interfering RNA (siRNA) in MC3T3-E1 cells. Following Orai1 downregulation, cell proliferation and cell cycle were examined. Furthermore, the expression of cyclin D1, cyclin E, CDK4, and CDK6 was analyzed. The activity of the Ras-NF-κB signaling pathway was investigated to identify the role of Orai1 in the regulation of osteoblast proliferation. Results: Orai1 was successfully downregulated in MC3T3-E1 cells by the Orai1 siRNA transfection (p <0.05). We found that MC3T3-E1 cell proliferation was decreased, and the cell cycle was arrested by Orai1 downregulation (p <0.05). Additionally, the expression of cyclin D1 was decreased by Orai1 downregulation (p <0.05), as was the activity of the Ras-NF-κB signaling pathway (p <0.05). Orai1 siRNA did not further reduce cell proliferation, the proportion of cells in the S phase, and cyclin D1 expression after chemical blockage of the Ras signaling pathway in MC3T3-E1 cells (p >0.05).Conclusions: The results reveal that Orai1 downregulation may reduce cyclin D1 expression by inactivating the Ras-NF-κB signaling pathway thus blocking osteoblast proliferation and cell cycle.

scholarly journals Orai1 Downregulation Causes Proliferation Reduction and Cell Cycle Arrest via Inactivation of the Ras-NF-κB Signaling Pathway in Osteoblasts

2021 ◽  
Author(s):  
Yunshan Guo ◽  
Dingjun Hao
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Signaling Pathway ◽  
Ras Signaling ◽  
Osteoblast Proliferation ◽  
Cycle Arrest ◽  
Reduce Cell Proliferation ◽  
Interfering Rna

Abstract Objective: The purpose of this study was to determine the role of Orai1 in the regulation of the proliferation and cell cycle of osteoblasts. Methods: The expression of Orai1 was inhibited by Orai1 small interfering RNA (siRNA) in MC3T3-E1 cells. Following Orai1 downregulation, cell proliferation and cell cycle were examined. Furthermore, the expression of cyclin D1, cyclin E, CDK4, and CDK6 was analyzed. The activity of the Ras-NF-κB signaling pathway was investigated to identify the role of Orai1 in the regulation of osteoblast proliferation. Results: Orai1 was successfully downregulated in MC3T3-E1 cells by the Orai1 siRNA transfection (p <0.05). We found that MC3T3-E1 cell proliferation was decreased, and the cell cycle was arrested by Orai1 downregulation (p <0.05). Additionally, the expression of cyclin D1 was decreased by Orai1 downregulation (p <0.05), as was the activity of the Ras-NF-κB signaling pathway (p <0.05). Orai1 siRNA did not further reduce cell proliferation, the proportion of cells in the S phase, and cyclin D1 expression after chemical blockage of the Ras signaling pathway in MC3T3-E1 cells (p >0.05).Conclusion: The results reveal that Orai1 downregulation may reduce cyclin D1 expression by inactivating the Ras-NF-κB signaling pathway thus blocking osteoblast proliferation and cell cycle.

scholarly journals Aberrant Expression of Nucleostemin Activates p53 and Induces Cell Cycle Arrest via Inhibition of MDM2

2008 ◽  
Vol 28 (13) ◽  
pp. 4365-4376 ◽  
Author(s):  
Mu-Shui Dai ◽  
Xiao-Xin Sun ◽  
Hua Lu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Arrest ◽  
Ribosomal Proteins ◽  
Cell Cycle Checkpoint ◽  
Aberrant Expression ◽  
Cycle Arrest ◽  
Reduce Cell Proliferation ◽  
Cycle Checkpoint ◽  
Dependent Cell

ABSTRACT The nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis. Both depletion and overexpression of NS reduce cell proliferation. However, the mechanisms underlying this regulation are still unclear. Here, we show that NS regulates p53 activity through the inhibition of MDM2. NS binds to the central acidic domain of MDM2 and inhibits MDM2-mediated p53 ubiquitylation and degradation. Consequently, ectopic overexpression of NS activates p53, induces G1 cell cycle arrest, and inhibits cell proliferation. Interestingly, the knockdown of NS by small interfering RNA also activates p53 and induces G1 arrest. These effects require the ribosomal proteins L5 and L11, since the depletion of NS enhanced their interactions with MDM2 and the knockdown of L5 or L11 abrogated the NS depletion-induced p53 activation and cell cycle arrest. These results suggest that a p53-dependent cell cycle checkpoint monitors changes of cellular NS levels via the impediment of MDM2 function.

scholarly journals miR-429 Suppresses Proliferation and Migration in Glioblastoma Cells and Induces Cell-cycle Arrest via Modulating Several Target Genes of ERBB Signaling Pathway

2021 ◽  
Author(s):  
Fatemeh Gheidari ◽  
Ehsan Arefian ◽  
Mahboubeh Kabiri ◽  
Ehsan Seyedjafari ◽  
Ladan Teimoori-Toolabi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Target Genes ◽  
Cycle Arrest ◽  
Cell Proliferation And Migration ◽  
Erbb Signaling ◽  
And Migration ◽  
Erbb Signaling Pathway ◽  
Proliferation And Migration

Abstract Glioblastoma is aggressive and lethal brain cancer, which is incurable by cancer standard treatments. miRNAs have great potential to be used for gene therapy due to their ability to modulate several target genes simultaneously. We found miR-429 is downregulated in glioblastoma and has several predicted target genes from the ERBB signaling pathway using bioinformatics tools. ERBB is the most over-activated genetic pathway in glioblastoma patients, which is responsible for augmented cell proliferation and migration in glioblastoma multiforme (GBM). Here we overexpressed miR-429 using lentiviral vectors in GBM U-251 cells and observed that the expression level of several oncogenes of the ERBB pathway, EGFR, PIK3CA, PIK3CB, KRAS, and MYC significantly decreased; as shown by real-time PCR and western blotting. Using the luciferase assay, we showed that miR-429 directly targets MYC, BCL2, and EGFR. In comparison to scrambled control, miR-429 had a significant inhibitory effect on cell proliferation and migration as deduced from MTT and scratch wound assays and induced cell-cycle arrest in flow cytometry. Altogether miR-429 seems to be an efficient suppressor of the ERBB genetic signaling pathway and a potential therapeutic for glioblastoma.

scholarly journals Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Rende Ning ◽  
Guang Chen ◽  
Run Fang ◽  
Yanhui Zhang ◽  
Wenjuan Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Osteosarcoma Cells ◽  
Antitumor Property ◽  
Human Osteosarcoma ◽  
Cycle Arrest ◽  
Stat3 Phosphorylation ◽  
Human Osteosarcoma Cells ◽  
M Phase

Abstract Background Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. Methods Colony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells. Results Diosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules. Conclusions These results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

scholarly journals Role of Interleukin-18 in Modulation of Oral Carcinoma Cell Proliferation

2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Athip Nilkaeo ◽  
Suthinee Bhuvanath
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Tumor Regression ◽  
Apoptotic Cell ◽  
Interleukin 18 ◽  
Cycle Arrest ◽  
Dose Dependent Fashion ◽  
Oral Cancer Cells

Interleukin-18 (IL-18), a proinflammatory cytokine, is produced by oral epithelia and carcinoma cells and implicated in tumor regression. Since its direct biological effect on oral cancer cells is not well defined, in this study, we employed a KB cell line to test IL-18 activity. Recombinant human IL-18 significantly inhibited KB cell proliferation in a dose-dependent fashion (P<.05) without increasing cytotoxicity. Analysis of its mode of action showed that IL-18 induced cell cycle arrest in the S phase; however, it did not trigger apoptotic cell death. Findings in this study indicate that the suppression of KB cell proliferation was attributed to the modulation of cell cycle progression, providing a new role of this cytokine in antitumor mechanisms.

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