CCNB1
G2/mitotic-specific cyclin-B1 [CCNB]
Publications[править]
If fertilization does not occur within a specific period of time, the quality of unfertilized oocytes in the oviduct (in vivo aging) or in culture (in vitro aging) will deteriorate over time. Icariin (ICA), found in all species of Epimedium herbs, has strong antioxidant activity and is thought to exert anti-aging effects in vitro. We asked whether ICA protects oocytes against age-related changes in vitro. We analyzed the reactive oxygen species (ROS) levels and expression of antioxidant, maternal, and estrogen receptor genes, and along with spindle morphology, and the developmental competence and quality of embryos in the presence and absence of ICA. Treatment with 5 µM ICA (ICA-5) led to a significant reduction in ROS activity, but increased mRNA expression of glutathione and antioxidant genes (SOD1, SOD2, PRDX5, and NFE2L2), during aging in vitro. In addition, ICA-5 prevented defects in spindle formation and chromosomal alignment, and increased mRNA expression of cytoplasmic maturation factor genes (BMP15, CCNB1, MOS, and GDF9). It also prevented apoptosis, increased mRNA expression of anti-apoptotic genes (BCL2L1 and BIRC5), and reduced mRNA expression of pro-apoptotic genes (BAK1 and CASP3). Although the maturation and cleavage rates were similar in all groups, the total cell number per blastocyst and the percentage of apoptotic cells at the blastocyst stage were higher and lower, respectively, in the control and ICA-5 groups than in the aging group. ICA protects oocytes against damage during aging in vitro; therefore, it can be used to improve assisted reproductive technologies.
Keywords
- Antioxidant
- Icariin
- In vitro Aging
- Oocyte
- Porcine
The citrus flavonoid hesperetin has a variety of pharmacological actions, including antioxidant, antiinflammatory, and anticancer activities. This study investigated whether hesperetin prevents aging of oocytes in vitro in which it determined the maturation of nuclear and cytoplasm and the developmental capacity of embryo by modulating the reactive oxygen species (ROS) level. Porcine oocytes were matured in vitro for 44 hr (control) and for an additional 24 hr in the presence of 0, 1, 10, 100, and 250 μM hesperetin (aging, H-1, H-10, H-100, and H-250, respectively). Although there was no difference in the rate of maturation among all the groups, both the control and H-100 groups significantly increased in the rate of cleavage and blastocyst formation compared to the aging group. The H-100 group significantly decreased ROS activity and increases the level of glutathione (GSH) and expression of the antioxidant genes (PRDX5, NFE2L, SOD1, and SOD2) compared with the aging group. The H-100 groups prevented aberrant spindle organization and chromosomal misalignment, blocked the decrease in the level of phosphorylated-p44/42 mitogen-activated protein kinase and increased the messenger RNA expression of cytoplasmic maturation factor genes (GDF9, CCNB1, BMP15, and MOS). Subsequently, both the control and H-100 groups significantly increased the total cell number and decreased the apoptosis cells at the blastocyst stage compared with aging group. The results indicate that hesperetin improves the quality of porcine oocytes by protecting them against oxidative stress during aging in vitro.
MeSH Terms
- Animals
- Blastocyst
- Cellular Senescence
- Embryonic Development
- Hesperidin
- Oocytes
- Oxidative Stress
- Reactive Oxygen Species
- Swine
Keywords
- aging in vitro
- antioxidant
- hesperetin
- oocyte
- porcine
Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase-9, caspase-3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β-Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase-9, caspase-3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase-9, caspase-3, p53, and p21. The shCCNB1 group had decreased proliferation and S-phase cell proportion and increased apoptosis, senescence, and G0/G1-phase cell proportion. The PFT-α group showed higher expressions of MDM2 and lower expressions of Bax, caspase-9, caspase-3, p53, and p21. The PFT-α group had increased proliferation and S-phase cell proportion and declined apoptosis, senescence, and G0/G1-phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.
MeSH Terms
- Aged
- Aging
- Apoptosis
- Cell Cycle
- Cell Line, Tumor
- Cell Proliferation
- Cyclin B1
- Female
- Gene Expression Regulation, Neoplastic
- Humans
- Male
- Middle Aged
- Neoplasm Proteins
- Pancreatic Neoplasms
- Signal Transduction
- Transfection
- Tumor Suppressor Protein p53
Keywords
- CCNB1
- apoptosis
- cell cycle
- gene silencing
- p53 signaling pathway
- pancreatic cancer
- senescence
Hypoxic culture is widely recognized as a method to efficiently expand human mesenchymal stem cells (MSCs) without loss of stem cell properties. However, the molecular basis of how hypoxia priming benefits MSC expansion remains unclear. In this report, our systemic quantitative proteomic and RT-PCR analyses revealed the involvement of hypoxic conditioning activated genes in the signaling process of the mitotic cell cycle. Introduction of screened two mitotic cyclins, CCNA2 and CCNB1, significantly extended the proliferation lifespan of MSCs in normoxic condition. Our results provide important molecular evidence that multipotency of human MSCs by hypoxic conditioning is determined by the mitotic cell cycle duration. Thus, the activation of mitotic cyclins could be a potential strategy to the application of stem cell therapy.
MeSH Terms
- Cell Differentiation
- Cell Hypoxia
- Cell Proliferation
- Humans
- Mesenchymal Stem Cells
- Up-Regulation
Keywords
- cell proliferation lifespan
- cyclin
- human mesenchymal stem cell
- hypoxia
- mitosis
- multipotency
Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.
MeSH Terms
- Adult
- Aging
- Animals
- Biomarkers, Tumor
- Breast Neoplasms
- Carcinogenesis
- Carcinoma, Ductal, Breast
- Carcinoma, Intraductal, Noninfiltrating
- Cohort Studies
- Computational Biology
- Disease Progression
- Female
- Gene Expression Regulation, Neoplastic
- Gene Regulatory Networks
- Genes, Neoplasm
- Genome, Human
- Humans
- Immunohistochemistry
- Mice
- Middle Aged
- Oligonucleotide Array Sequence Analysis
- Reproducibility of Results
- Species Specificity
- Transcriptome
- Young Adult