Phosphorylation of cyclin O, a novel cyclin family protein containing a cyclin-like domain, is involved in the activation of cyclin-dependent kinase 2

Kim, Do-Hyung; Park, Jong‐Hwa; Lee, Bora; Jang, Kyoung Ok; Chung, In Sik; Han, Ye

doi:10.3892/ol.2014.2530

Cited by 7 publications

(5 citation statements)

References 15 publications

(18 reference statements)

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“…It has been demonstrated that cyclins play an important role in regulating the cell cycle and apoptosis. 24 , 25 CCNO could regulate CDK2 kinase activity through the phosphorylation of the 81st serine residue, 26 and induce the intrinsic apoptotic signaling pathway in lymphoid cells in concert with CDK2. 11 …”

Section: Discussionmentioning

confidence: 99%

Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis

Li¹,

Cao²,

Zhou³

et al. 2018

OTT

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PurposeRecently, Cyclin O (CCNO) has been reported to be a novel protein of the cyclin family. However, the clinical significance and functional roles of CCNO in human cancer, including gastric cancer (GC), remain largely unexplored. In this study, we investigated the clinical and functional roles of CCNO in GC.MethodsWe analyzed CCNO expression patterns in GC patients. To investigate the role of CCNO in malignancy of GC, we used lentivirus-delivered short hairpin RNA to knockdown CCNO expression in GC cell lines. Then multiparametric high-content screening and MTT incorporation assay were used to assess the cell proliferation capability. Cell apoptosis was detected by flow cytometry and Caspase 3/7 assays. Furthermore, the effect of CCNO on tumorigenicity of GC was also determined in vivo. Finally, microarray analysis was performed to elucidate the molecular mechanisms by which shCCNO inhibited the malignancy of GC cells.ResultsThe analysis from The Cancer Genome Atlas database revealed elevated CCNO mRNA expression in GC tissue than in the adjacent normal tissue. Immunohistochemical studies also showed that stronger cytoplasmic staining of CCNO was detected in GC tissues. Downregulation of CCNO in GC cells efficiently, through infection with the lentivirus-mediated specific short hairpin RNA, could significantly induce cell apoptosis and inhibit the proliferative properties both in vitro and in vivo. Microarray analysis further revealed 652 upregulated genes and 527 downregulated genes in the shCCNO group compared with control, and indicated that CCNO knockdown could inhibit the malignancy of GC cells through inducing genome-wide gene expression changes.ConclusionOur work is the first to reveal that elevated CCNO expression is closely associated with human GC development and that CCNO knockdown could efficiently inhibit the malignant properties of GC cells by inducing cell apoptosis. Therefore, CCNO could be used as a potential biomarker for prognosis or even as a therapeutic target in human GC.

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Section: Discussionmentioning

confidence: 99%

Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis

Li¹,

Cao²,

Zhou³

et al. 2018

OTT

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“…At the same time, it is necessary to look at the expression of cyclin and cyclin-dependent kinase (CDK). 28 Different cyclin subtypes activate CDK to regulate the cell cycle. Some oncoproteins, tumor suppressor proteins and transcription factors can act on the promoter region of CyclinD1 and regulate the expression of CyclinD1.At different stages, if the expression of cyclin increases, G0/G1 quickly enters S phase and G2/M phase, and the proportion of G0/G1 cells decreases, which is the result of cell cycle activation.…”

Section: Discussionmentioning

confidence: 99%

Effect of fenofibrate on proliferation of SMMC-7721 cells via regulating cell cycle

Jiang

et al. 2021

Hum Exp Toxicol

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Liver cancer is a malignant cancer with great harmfulness. Fenofibrate is a peroxisome proliferation activated receptor (PPARα) agonist widely used in the treatment of dyslipidemia. Previous studies have shown that fenofibrate may promote cell proliferation, but the underlying mechanism has not been fully characterized. The aim of this study was to investigate the role of PPARα agonist fenofibrate in cell proliferation of SMMC-7721 cells compared with that of THLE-2 cells. SMMC-7721 and THLE-2 cells were treated with different concentrations of fenofibrate. Cell proliferation was analyzed by MTT, using flow cytometry for cell cycle analysis, and CyclinD1, Cyclin-dependent kinases2 (CDK2) and Proliferating Cell Nuclear Antigen (PCNA) were analyzed by Western blotting. RT-qPCR method was used to assess CDK2, CyclinD1 and PCNA mRNA levels. The results showed that 10−9–10−4 mol/L fenofibrate could induce cell growth and 10−4, 10−5, 10−6 mol/L fenofibrate could reduce the number of G0/G1 phase cells and increased in the number of cells in S and G2/M phase of cell cycle in SMMC-7721 cells. Furthermore, fenofibrate could significantly increase the expression of cell cycle related protein (CyclinD1, CDK2)and cell proliferation related proteins (PCNA). The use of PPARα inhibitor MT886 inhibited cell cycle progression and promote tumor cell apoptosis. But fenofibrate had no obvious effect on THLE-2 cells. These results revealed the effect of fenofibrate on the cell cycle of liver cancer cells, and provided a reasonable explanation for studying how fenofibrate promotes cell proliferation.

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“…Immunoprecipitation of the kallistatin complex with its binding protein was performed as previously described [28]. The whole-cell lysate of NCI-H446 cells was pretreated with protein A-Sepharose beads for 1 h at 4 °C with rotation.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of integrin β3, a binding partner of kallistatin, leads to reduced viability, invasion and proliferation in NCI-H446 cells

Wang

Huang

et al. 2016

Cancer Cell Int

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BackgroundKallistatin is a serine proteinase inhibitor and heparin-binding protein. It is considered an endogenous angiogenic inhibitor. In addition, multiple studies demonstrated that kallistatin directly inhibits cancer cell growth. However, the molecular mechanisms underlying these effects remain unclear.MethodsPull-down, immunoprecipitation, and immunoblotting were used for binding experiments. To elucidate the mechanisms, integrin β3 knockdown (siRNA) or blockage (antibody treatment) on the cell surface of small the cell lung cancer NCI-H446 cell line was used.ResultsInterestingly, kallistatin was capable of binding integrin β3 on the cell surface of NCI-H446 cells. Meanwhile, integrin β3 knockdown or blockage resulted in loss of antitumor activities induced by kallistatin. Furthermore, kallistatin suppressed tyrosine phosphorylation of integrin β3 and its downstream signaling pathways, including FAK/-Src, AKT and Erk/MAPK. Viability, proliferation and migration of NCI-H446 cells were inhibited by kallistatin, with Bcl-2 and Grb2 downregulation, and Bax, cleaved caspase-9 and caspase 3 upregulation.ConclusionsThese findings reveal a novel role for kallistatin in preventing small cell lung cancer growth and mobility, by direct interaction with integrin β3, leading to blockade of the related signaling pathway.

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Phosphorylation of cyclin O, a novel cyclin family protein containing a cyclin-like domain, is involved in the activation of cyclin-dependent kinase 2

Cited by 7 publications

References 15 publications

Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis

Knockdown of CCNO decreases the tumorigenicity of gastric cancer by inducing apoptosis

Effect of fenofibrate on proliferation of SMMC-7721 cells via regulating cell cycle

Inhibition of integrin β3, a binding partner of kallistatin, leads to reduced viability, invasion and proliferation in NCI-H446 cells

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