scholarly journals Identification of CDCA8, DSN1 and BIRC5 in Regulating Cell Cycle and Apoptosis in Osteosarcoma Using Bioinformatics and Cell Biology

2020 ◽  
Vol 19 ◽  
pp. 153303382096560
Author(s):  
Qinwen Li ◽  
Jie Liang ◽  
Bo Chen
Keyword(s):  
Cell Cycle ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Osteosarcoma Cells ◽  
Apoptosis Pathway ◽  
Protein Protein Interaction ◽  
Limma Package ◽  
Key Genes ◽  
Cycle Regulation

Introduction: Osteosarcoma is the most common primary tumor of bone, although some molecular markers have been identified, the detailed molecular mechanisms underlying osteosarcoma are currently not fully understood. In the present study, we attempted to identify the potential key genes and pathways in osteosarcoma using bioinformatics analysis. Methods: GSE14359 was downloaded from the GEO database, and analyzed using Limma package. Gene Ontology and pathway enrichment analyses of the DEGs were performed in the DAVID database, followed by the construction of a protein–protein interaction (PPI) network with software Cytoscape, subnetwork modules were subsequently identified and analyzed, and further validation in human osteosarcoma tissues and osteosarcoma cells line was performed. Results: 964 Differentially expressed genes (DEGs) identified, of which 222 were up-regulated and 742 were down-regulated. Among them, 10 genes (including BIRC5, MAD2L1, Bub1, DSN1, SPC24, CDCA8, STAG2, CENPA, MLF1IP and Mis12) were identified as hub genes and they were mainly enriched in pathways, including mRNA surveillance, RNA transport and PI3K-Akt signaling pathways. Further validation indicated 6 gene (DSN1, BIRC5, CDCA8, MLF1IP, MAD2L1 and SPC24) is highly expressed in osteosarcoma tissues. Among them, CDCA8, DSN1 and BIRC5 significantly promoted the proliferation of osteosarcoma cells in vitro. In terms of mechanism, DSN1 and CDCA8 were mainly involved in cell cycle regulation, while BIRC5 was mainly involved in the regulation of apoptosis pathway. Conclusions: We identified some key genes and pathways in osteosarcoma, which might be used as molecular targets or diagnostic biomarker for the diagnosis and therapy of osteosarcoma.

The emerging importance of cyclin-dependent kinase inhibitors in the regulation of the plant cell cycle and related processesThis review is one of a selection of papers published in the Special Issue on Plant Cell Biology.

2006 ◽  
Vol 84 (4) ◽  
pp. 640-650 ◽  
Author(s):  
Hong Wang ◽  
Yongming Zhou ◽  
Larry C. Fowke
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Plant Cell ◽  
Cell Biology ◽  
Cell Cycle Regulation ◽  
Cellular Localization ◽  
Molecular Mechanisms ◽  
Cdk Inhibitors ◽  
Cyclin Dependent Kinase ◽  
Cycle Regulation

The cell division cycle in plants as in other eukaryotes is controlled by the cyclin-dependent kinase (CDK). This CDK paradigm determines that developmental cues and environmental signals need to impinge on the CDK complex to affect the cell cycle. An important part of understanding cell cycle regulation is to understand how CDK is regulated by various factors. In addition, there are features that set the cell cycle regulation in plants apart from that in other eukaryotes such as animals. Our knowledge of the molecular mechanisms that underlie the differences is poor. A family of plant CDK inhibitor proteins has been identified. The plant CDK inhibitors share similarity with a family of animal CDK inhibitors in a small region, while most of the sequence and the structural layout of the plant CDK inhibitors are different from the animal counterparts. Studies of plant CDK inhibitors have been performed mostly with the CDK inhibitors from Arabidopsis called ICKs (also referred to as KRPs). ICKs interact with D-type cyclins and A-type CDK. Overexpression of ICKs has been shown to affect cell division, plant growth, and morphogenesis. Studies of ICKs have also provided insightful information on the control of endoreduplication in plants. These aspects as well as cellular localization and protein regulation of ICKs are reviewed.

scholarly journals Huaier Extract Inhibits Proliferation and Promotes Apoptosis via the MAPK Pathway in Human Osteosarcoma Cells

2021 ◽  
Author(s):  
Xin Guan ◽  
Yaxi Zhai ◽  
Rong Tang ◽  
Panpan Yang ◽  
Dongfang Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Mapk Pathway ◽  
Inhibitory Effect ◽  
Cell Cycle Distribution ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Invasion And Migration ◽  
Human Osteosarcoma Cells

Abstract Background: Osteosarcoma is a common pediatric bone malignancy. Huaier, a traditional Chinese medicine, attracts increasing attention for its antitumor effect. The aim of this study is to investigate the inhibitory effect and molecular mechanisms of Huaier in osteosarcoma cells. Methods: Bioinformatics was performed to determine the biological processes and pathways connected to Huaier. The CCK-8 method and flow cytometry were used to detect the cell viability, cell cycle distribution and apoptosis of osteosarcoma cells (MG-63 and MNNG/HOS). Western blot was applied to assess the expression of proteins involved in apoptosis, cell cycle and the MAPK pathway. Results: Huaier could inhibit osteosarcoma cells proliferation by arresting cells in the G0/G1 phase. The extract also suppressed invasion and migration, while promoting the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Under Huaier stimulation, the expression of p-ERK/ERK, Cyclin D1 and Bcl-2 decreased, while the expression of p-JNK/JNK, p-P38/P38, P21, P27, Bax and Caspase3 increased in osteosarcoma cells. Conclusions: Our findings demonstrated for the first time that Huaier extract could inhibit proliferation and promote apoptosis in osteosarcoma cells via the MAPK pathway in vitro, suggesting that Huaier may be developed as a chemopreventive medicine for the treatment of osteosarcoma.

scholarly journals Progress in understanding the role of lncRNA in programmed cell death

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Na Jiang ◽  
Xiaoyu Zhang ◽  
Xuejun Gu ◽  
Xiaozhuang Li ◽  
Lei Shang
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Molecular Mechanisms ◽  
Membrane Receptors ◽  
Gene Expressions ◽  
Apoptosis Pathway ◽  
Stem Cell Pluripotency ◽  
Extrinsic Apoptosis ◽  
Related Proteins ◽  
Cycle Regulation

AbstractLong non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides but not translated into proteins. LncRNAs regulate gene expressions at multiple levels, such as chromatin, transcription, and post-transcription. Further, lncRNAs participate in various biological processes such as cell differentiation, cell cycle regulation, and maintenance of stem cell pluripotency. We have previously reported that lncRNAs are closely related to programmed cell death (PCD), which includes apoptosis, autophagy, necroptosis, and ferroptosis. Overexpression of lncRNA can suppress the extrinsic apoptosis pathway by downregulating of membrane receptors and protect tumor cells by inhibiting the expression of necroptosis-related proteins. Some lncRNAs can also act as competitive endogenous RNA to prevent oxidation, thereby inhibiting ferroptosis, while some are known to activate autophagy. The relationship between lncRNA and PCD has promising implications in clinical research, and reports have highlighted this relationship in various cancers such as non-small cell lung cancer and gastric cancer. This review systematically summarizes the advances in the understanding of the molecular mechanisms through which lncRNAs impact PCD.

scholarly journals Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Satoshi Takagi ◽  
Yuki Sasaki ◽  
Sumie Koike ◽  
Ai Takemoto ◽  
Yosuke Seto ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Pulmonary Metastasis ◽  
Lysophosphatidic Acid ◽  
Therapeutic Intervention ◽  
Molecular Mechanisms ◽  
Morphological Changes ◽  
Osteosarcoma Cells ◽  
Invasion And Metastasis ◽  
Platelet Releasate

AbstractOsteosarcoma is the most common primary malignant bone cancer, with high rates of pulmonary metastasis. Osteosarcoma patients with pulmonary metastasis have worse prognosis than those with localized disease, leading to dramatically reduced survival rates. Therefore, understanding the biological characteristics of metastatic osteosarcoma and the molecular mechanisms of invasion and metastasis of osteosarcoma cells will lead to the development of innovative therapeutic intervention for advanced osteosarcoma. Here, we identified that osteosarcoma cells commonly exhibit high platelet activation-inducing characteristics, and molecules released from activated platelets promote the invasiveness of osteosarcoma cells. Given that heat-denatured platelet releasate maintained the ability to promote osteosarcoma invasion, we focused on heat-tolerant molecules, such as lipid mediators in the platelet releasate. Osteosarcoma-induced platelet activation leads to abundant lysophosphatidic acid (LPA) release. Exposure to LPA or platelet releasate induced morphological changes and increased invasiveness of osteosarcoma cells. By analyzing publicly available transcriptome datasets and our in-house osteosarcoma patient-derived xenograft tumors, we found that LPA receptor 1 (LPAR1) is notably upregulated in osteosarcoma. LPAR1 gene KO in osteosarcoma cells abolished the platelet-mediated osteosarcoma invasion in vitro and the formation of early pulmonary metastatic foci in experimental pulmonary metastasis models. Of note, the pharmacological inhibition of LPAR1 by the orally available LPAR1 antagonist, ONO-7300243, prevented pulmonary metastasis of osteosarcoma in the mouse models. These results indicate that the LPA–LPAR1 axis is essential for the osteosarcoma invasion and metastasis, and targeting LPAR1 would be a promising therapeutic intervention for advanced osteosarcoma.

scholarly journals LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Chen-Hua Dong ◽  
Tao Jiang ◽  
Hang Yin ◽  
Hu Song ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Gene Set Enrichment Analysis ◽  
Molecular Therapy ◽  
Cycle Progression ◽  
Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

scholarly journals Screen Key Genes Associated with Distraction-Induced Osteogenesis of Stem Cells Using Bioinformatics Methods

2021 ◽  
Vol 22 (12) ◽  
pp. 6505
Author(s):  
Jishizhan Chen ◽  
Jia Hua ◽  
Wenhui Song
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Negative Control ◽  
Gene Set Enrichment Analysis ◽  
Venn Diagram ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Two Samples ◽  
Key Genes

Applying mesenchymal stem cells (MSCs), together with the distraction osteogenesis (DO) process, displayed enhanced bone quality and shorter treatment periods. The DO guides the differentiation of MSCs by providing mechanical clues. However, the underlying key genes and pathways are largely unknown. The aim of this study was to screen and identify hub genes involved in distraction-induced osteogenesis of MSCs and potential molecular mechanisms. Material and Methods: The datasets were downloaded from the ArrayExpress database. Three samples of negative control and two samples subjected to 5% cyclic sinusoidal distraction at 0.25 Hz for 6 h were selected for screening differentially expressed genes (DEGs) and then analysed via bioinformatics methods. The Gene Ontology (GO) terms and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were investigated. The protein–protein interaction (PPI) network was visualised through the Cytoscape software. Gene set enrichment analysis (GSEA) was conducted to verify the enrichment of a self-defined osteogenic gene sets collection and identify osteogenic hub genes. Results: Three hub genes (IL6, MMP2, and EP300) that were highly associated with distraction-induced osteogenesis of MSCs were identified via the Venn diagram. These hub genes could provide a new understanding of distraction-induced osteogenic differentiation of MSCs and serve as potential gene targets for optimising DO via targeted therapies.

scholarly journals Ionic Dissolution Products of NovaBone® Promote Osteoblastic Proliferation via Influences on the Cell Cycle

2009 ◽  
Vol 37 (3) ◽  
pp. 737-745 ◽  
Author(s):  
Z Qiu ◽  
H Yang ◽  
J Wu ◽  
L Wei ◽  
J Li
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Cultured Cells ◽  
Bone Morphogenic Protein ◽  
Mg63 Cells ◽  
Silicon Ions ◽  
Cycle Regulation ◽  
Bone Morphogenic Protein 2 ◽  
Cells Cultured

This study investigated the effects of the ionic dissolution products of NovaBone® on osteoblastic proliferation and cell cycle regulation. MG63 osteoblast-like cells were cultured in NovaBone®-conditioned Dulbecco's Modified Eagle's Medium (DMEM) or control DMEM for 10 days. The concentration of silicon ions was significantly higher in NovaBone®-conditioned DMEM than control DMEM. MG63 cells cultured in NovaBone®-conditioned DMEM exhibited greater proliferation on days 1 and 4 than control cells. There were increased proportions of Novabone®-conditioned DMEM-cultured cells in the S and G2/M phases, and decreased proportions in the G0/G1 phase on days 1 and 4 versus control cells, while no differences were observed on days 7 and 10 between the two groups. Bone morphogenic protein 2 production increased in both groups, but was significantly higher for the NovaBone®-conditioned DMEM-cultured cells on day 10 compared with the controls. In conclusion, the NovaBone® ionic dissolution products, particularly the silicon ions, promoted proliferation of MG63 osteoblast-like cells in vitro via influences on the cell cycle.

Age-associated features of the expression level of apoptosis markers in cardiomyocytes of patients with dilated cardiomyopathy

2022 ◽  
pp. 885-890
Author(s):  
К.П. Кравченко ◽  
К. Л. Козлов ◽  
А.О. Дробинцева ◽  
Д.С. Медведев ◽  
В.О. Полякова
Keyword(s):  
Cell Death ◽  
Dilated Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Confocal Laser ◽  
Control Group ◽  
Cellular Mechanisms ◽  
Apoptosis Pathway ◽  
Bax Protein

Для понимания патогенеза дилатационной кардиомиопатии (ДКМП) необходимо установить молекулярно-клеточные механизмы старения миокарда, в том числе связанные с программируемой клеточной гибелью, молекулярные механизмы которого практически не изучены. Цель работы - изучение маркеров апоптоза в кардиомиоцитах у пациентов с ДКМП in vitro. В работе использовали метод первичных диссоциированных клеточных культур и метод иммунофлюоресцентной конфокальной лазерной микроскопии. Для моделирования клеточного старения использовали клетки 3-го и 14-го пассажей, соответствующие «молодым» и «старым» культурам. На молекулярном уровне старение клеток кардиомиоцитов сопровождалось повышением экспрессии р16 в 2 раза по сравнению с «молодыми культурами» как в контрольной, так и в группе с ДКМП. Также установлено, что экспрессия р16 в культурах, взятых от пациентов с патологией, была в 2 раза выше, чем в аналогичных культурах от здоровых пациентов. Экспрессия р21 была повышена в группе с ДКМП по сравнению с контрольной группой, однако при старении культуры экспрессия p21 не изменялась, оставаясь на высоком уровне. Наиболее значимые различия были получены при сравнении экспрессии Bax в культуре клеток кардиомиоцитов из группы с ДКМП в «молодой» культуре с нормой - в 3,2 раза. Старение клеток миокарда на молекулярном уровне проявлялось в повышении экспрессии белка Baх, именно он является запускающим механизмом митохондриального пути апоптоза. Возможно, этот путь клеточной гибели является превалирующем при ДКМП. To understand the pathogenesis of dilated cardiomyopathy (DCMP), it is necessary to establish the molecular-cellular mechanisms of myocardial aging, including those associated with programmed cell death, the molecular mechanisms of which have not been practically studied. The aim of this work is to study markers of apoptosis in cardiomyocytes of patients with DCMP in vitro. We used the method of primary dissociated cell cultures and the method of immunofluorescence confocal laser microscopy. Cells of the 3 and 14 passages, corresponding to «young» and «old» cultures, were used to simulate cellular senescence. Results. At the molecular level, aging of cardiomyocyte cells was accompanied by a twofold increase in the expression of p16 compared to «young cultures» both in the control group and in the group with DCMP. It was also found that the expression of p16 in cultures taken from patients with pathology was 2 times higher than in similar cultures from healthy patients. The expression of p21 was increased in the group with DCMP compared to the control; however, with aging of the culture, the expression of p21 did not change, remaining at a significant level. The most significant differences were obtained when comparing the expression of Bax in the cell culture of cardiomyocytes from the group with DCMP in a «young» culture compared with the norm, 3,2 times. Aging of myocardial cells at the molecular level was manifested in an increase in the expression of the Bax protein, which is the triggering mechanism of the mitochondrial apoptosis pathway. It is possible that this pathway of cell death is prevalent in DCMP.

scholarly journals Epigenetic Regulation of Apoptosis and Cell Cycle in Osteosarcoma

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Krithi Rao-Bindal ◽  
Eugenie S. Kleinerman
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Molecular Mechanisms ◽  
Genetic Mutations ◽  
Epigenetic Mechanisms ◽  
Epigenetic Alterations ◽  
Novel Therapeutic Strategies ◽  
Cycle Regulation ◽  
Insight Into

The role of genetic mutations in the development of osteosarcoma, such as alterations in p53 and Rb, is well understood. However, the significance of epigenetic mechanisms in the progression of osteosarcoma remains unclear and is increasingly being investigated. Recent evidence suggests that epigenetic alterations such as methylation and histone modifications of genes involved in cell cycle regulation and apoptosis may contribute to the pathogenesis of this tumor. Importantly, understanding the molecular mechanisms of regulation of these pathways may give insight into novel therapeutic strategies for patients with osteosarcoma. This paper serves to summarize the described epigenetic mechanisms in the tumorigenesis of osteosarcoma, specifically those pertaining to apoptosis and cell cycle regulation.

Sign in / Sign up

Export Citation Format

Share Document