scholarly journals DNA Methylation Mediated Downregulation of miR-449c Controls Osteosarcoma Cell Cycle Progression by Directly Targeting Oncogene c-Myc

2017 ◽  
Vol 13 (8) ◽  
pp. 1038-1050 ◽  
Author(s):  
Qing Li ◽  
Hua Li ◽  
Xueling Zhao ◽  
Bing Wang ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Cell Cycle Progression ◽  
Osteosarcoma Cell ◽  
Cycle Progression

DNA methylation in Caulobacter and other Alphaproteobacteria during cell cycle progression

2014 ◽  
Vol 22 (9) ◽  
pp. 528-535 ◽  
Author(s):  
Saswat S. Mohapatra ◽  
Antonella Fioravanti ◽  
Emanuele G. Biondi
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
Cell Cycle Progression ◽  
Cycle Progression

scholarly journals The tankyrase-specific inhibitor JW74 affects cell cycle progression and induces apoptosis and differentiation in osteosarcoma cell lines

2013 ◽  
Vol 3 (1) ◽  
pp. 36-46 ◽  
Author(s):  
Eva Wessel Stratford ◽  
Jeanette Daffinrud ◽  
Else Munthe ◽  
Russell Castro ◽  
Jo Waaler ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Specific Inhibitor ◽  
Osteosarcoma Cell ◽  
Cycle Progression

scholarly journals In silico APC/C substrate discovery reveals cell cycle degradation of chromatin regulators including UHRF1

2020 ◽  
Author(s):  
Jennifer L. Kernan ◽  
Raquel C. Martinez-Chacin ◽  
Xianxi Wang ◽  
Rochelle L. Tiedemann ◽  
Thomas Bonacci ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
In Silico ◽  
Cell Cycle Progression ◽  
Vital Role ◽  
Regulatory Proteins ◽  
Phase Cell ◽  
Cell Physiology ◽  
Cycle Progression ◽  
Chromatin Regulator

AbstractThe Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substrates in silico. This analysis identified many known substrates and suggested numerous candidates. Unexpectedly, chromatin regulatory proteins are enriched among putative substrates and we show that several chromatin proteins bind APC/C, oscillate during the cell cycle and are degraded following APC/C activation, consistent with being direct APC/C substrates. Additional analysis revealed detailed mechanisms of ubiquitylation for UHRF1, a key chromatin regulator involved in histone ubiquitylation and DNA methylation maintenance. Disrupting UHRF1 degradation at mitotic exit accelerates G1-phase cell cycle progression and perturbs global DNA methylation patterning in the genome. We conclude that APC/C coordinates crosstalk between cell cycle and chromatin regulatory proteins. This has potential consequences in normal cell physiology, where the chromatin environment changes depending on proliferative state, as well as in disease.

scholarly journals NUSAP1 Accelerates Osteosarcoma Cell Proliferation and Cell Cycle Progression via Upregulating CDC20 and Cyclin A2

2021 ◽  
Vol Volume 14 ◽  
pp. 3443-3454
Author(s):  
Haoran Wang ◽  
Zixiang Liu ◽  
Peng Wu ◽  
Hanqing Wang ◽  
Weiwei Ren
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Osteosarcoma Cell ◽  
Cycle Progression ◽  
Cyclin A2

Centrosome Aberrations, Disturbed Mitotic Spindle Formation and G1 Arrest in Normal and Leukemic Cells Treated with the SRC/ABL Inhibitor Dasatinib.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2167-2167
Author(s):  
Alice Fabarius ◽  
Michelle Giehl ◽  
Alwin Kraemer ◽  
Oliver Frank ◽  
Martin C. Mueller ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Dermal Fibroblasts ◽  
G1 Arrest ◽  
Osteosarcoma Cell ◽  
Cycle Progression ◽  
Spindle Formation

Abstract Multitargeted ABL inhibitors have been developed to simultaneously inhibit various pathways associated with proliferation in BCR-ABL+ diseases. Dasatinib (Bristol Myers Squibb) is a potent inhibitor targeting ABL, SRC, and other tyrosine kinases. SRC kinases are required for progression through the initial phase of mitosis. Centrosomes play a fundamental role in mitotic spindle organization, chromosome segregation and genetic stability. We sought to evaluate the activity of dasatinib on proliferation, centrosome status, spindle formation, and cell cycle progression in vitro and in vivo. Normal human dermal fibroblasts (NHDF), Chinese hamster embryonal fibroblasts (CHE), and the human osteosarcoma cell line U2OS were treated with serial concentrations (1nM-10μM) of dasatinib for 3 weeks. Effects of dasatinib were compared with data achieved with the ABL inhibitors imatinib (Novartis, 5–20μM) and nilotinib (Novartis, 0.5–20μM), the specific SRC inhibitor PP2 (Calbiochem-Novabiochem, 0.1–2μM), the ABL/LYN inhibitor INNO-406 (Innovive, 0.1–2μM), and solvent control. Bone marrow and peripheral blood samples from 18 patients (pts, 10 m, 8 f; median age 57 yrs, range 26–75) treated with dasatinib (70mg bid) after imatinib failure for a median of 11 mo (range, 3–16) were investigated. 17 pts had chronic myeloid leukemia (CML) in chronic phase. One patient suffered from a gastrointestinal stromal tumor. For comparison, 3 untreated CML pts and 3 healthy individuals were evaluated. Cell proliferation was determined in liquid culture incubated with serial dilutions of the inhibitor. Centrosome morphology and spindle formation were evaluated after pericentrin and α-tubulin staining, respectively. Cell cycle progression was analyzed by FACS and expression of EG5 by immunofluorescence microscopy. Dasatinib induced a G1 cell cycle arrest in all cell lines tested and in pts associated with a shift to 1n DNA ploidy and absence of EG5 as a marker for G2 phase/mitosis. In vitro, centrosomal aberrations and delay of spindle formation were observed in a dose dependent fashion. In pts, centrosome alterations were found in a median of 17% (range, 10–15) of cells. Disturbed spindle formation was observed in 9/18 pts. In comparison, incubation with imatinib and nilotinib was associated with centrosome aberrations but not with defects of spindle formation and G1 arrest. PP2 induced S-phase arrest; centrosome aberrations were observed at higher dosages (1–2 μM) only, spindle formation was not affected. INNO-406 was associated with both centrosome aberrations and disturbed spindle formation. In pharmacological doses, proliferation of BCR-ABL neg. cell lines was inhibited after dasatinib treatment, but not after incubation with imatinib, nilotinib, PP2, or INNO-406. In conclusion, dasatinib blocks the G1/S transition and thereby inhibits cell growth in normal and neoplastic cells. In addition, it induces both centrosomal and spindle aberrations. Effects of dasatinib are not based on SRC inhibition alone but may be associated with the combination of SRC and ABL inhibition or with non-specific effects on multiple kinases. Therefore, dasatinib should be defined as a cytostatic drug with a strong targeted component resulting in a preferential inhibition of cells harboring a specific target, like BCR-ABL.

scholarly journals Upregulation of microRNA-23b-3p induced by farnesoid X receptor regulates the proliferation and apoptosis of osteosarcoma cells

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Bin Wu ◽  
Chengjuan Xing ◽  
Juan Tao
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Farnesoid X Receptor ◽  
Cell Cycle Distribution ◽  
Osteosarcoma Cell ◽  
Potent Effect ◽  
Cycle Progression ◽  
Apoptosis Rate ◽  
Proliferation And Apoptosis

Abstract Background The downstream targets of farnesoid X receptor (FXR) such as miRNAs have a potent effect on the progression of many types of cancer. We aim to study the effects of FXR on osteosarcoma (OS) development and the potential role of microRNA-23b-3p. Methods The expressions of FXR and miR-23b-3p in normal osteoblasts and five osteosarcoma cell lines were measured. Their correlations were analyzed by Pearson’s test and verified by the introduction of FXR agonist, GW4064. TargetScan predicted that cyclin G1 (CCNG1) was a target for miR-23b-3p. The transfection of FXR siRNA was performed to confirm the correlation between FXR and miR-23b-3p. We further transfected miR-23b-3p inhibitor into MG-63 cells, and the transfected cells were treated with 5 μM GW4064 for 48 h. Quantitative PCR (qPCR) and Western blot were performed for expression analysis. Cell proliferation, cell apoptosis rate, and cell cycle distribution were assessed by clone formation assay and flow cytometry. Results Scatter plot showed a positive correlation between FXR and miR-23b-3p (Pearson’s coefficient test R2 = 1.00, P = 0.0028). As CCNG1 is a target for miR-23b-3p, the treatment of GW4064 induced the downregulation of CCNG1 through upregulating miR-23b-3p. The inhibition of miR-23b-3p obviously promoted cell viability, proliferation, and cell cycle progression but reduced apoptosis rate of MG-63 cells; however, the treatment of GW4064 could partially reverse the effects of the inhibition of miR-23b-3p on OS cells. Conclusions Upregulated FXR by GW4064 can obviously suppress OS cell development, and the suppressive effects may rely on miR-23b-3p/CCNG1 pathway.

MiR-223/Ect2/p21 signaling regulates osteosarcoma cell cycle progression and proliferation

2013 ◽  
Vol 67 (5) ◽  
pp. 381-386 ◽  
Author(s):  
Jianli Xu ◽  
Qi Yao ◽  
Yu Hou ◽  
Meng Xu ◽  
Sheng Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Osteosarcoma Cell ◽  
Cycle Progression

scholarly journals In silico APC/C substrate discovery reveals cell cycle-dependent degradation of UHRF1 and other chromatin regulators

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000975
Author(s):  
Jennifer L. Franks ◽  
Raquel C. Martinez-Chacin ◽  
Xianxi Wang ◽  
Rochelle L. Tiedemann ◽  
Thomas Bonacci ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Methylation ◽  
In Silico ◽  
Cell Cycle Progression ◽  
Vital Role ◽  
Regulatory Proteins ◽  
Phase Cell ◽  
Cell Physiology ◽  
Cycle Progression ◽  
Cycle Dependent

The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase and critical regulator of cell cycle progression. Despite its vital role, it has remained challenging to globally map APC/C substrates. By combining orthogonal features of known substrates, we predicted APC/C substrates in silico. This analysis identified many known substrates and suggested numerous candidates. Unexpectedly, chromatin regulatory proteins are enriched among putative substrates, and we show experimentally that several chromatin proteins bind APC/C, oscillate during the cell cycle, and are degraded following APC/C activation, consistent with being direct APC/C substrates. Additional analysis revealed detailed mechanisms of ubiquitylation for UHRF1, a key chromatin regulator involved in histone ubiquitylation and DNA methylation maintenance. Disrupting UHRF1 degradation at mitotic exit accelerates G1-phase cell cycle progression and perturbs global DNA methylation patterning in the genome. We conclude that APC/C coordinates crosstalk between cell cycle and chromatin regulatory proteins. This has potential consequences in normal cell physiology, where the chromatin environment changes depending on proliferative state, as well as in disease.

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