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Results for “Cyclin B1”

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6 recordsLinked to original sources
PubMed2026

Analysis of the molecular mechanism underlying di(2-ethylhexyl) phthalate-induced bladder carcinogenesis via network toxicology and molecular docking approaches: An observational study.

This study aims to investigate the toxicity of di(2-ethylhexyl) phthalate (DEHP) and the potential molecular mechanisms of DEHP-induced bladder cancer (BLCA) using network toxicology and molecular docking strategies. The toxicity of DEHP was assessed using Prox-II software, and potential targets for DEHP-induced BLCA were identified by integrating data from ChEMBL database, Search Tool for Interactions of Chemicals, SwissTargetPrediction, GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas. STRING database and Cytoscape were employed to construct target networks and determine core targets. The expression levels of core targets were analyzed using R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on potential and core targets. Molecular docking was carried out using CB-Dock 2 to verify the interactions between DEHP and core targets. A total of 105 potential targets related to DEHP-induced BLCA were identified, from which 7 core targets were selected: cyclin-dependent kinase 1, interleukin 6, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, cyclin B2, and B-cell lymphoma 2. IL-6 and B-cell lymphoma 2 showed downregulated expression in tumor tissues, while cyclin-dependent kinase 1, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, and cyclin B2 were upregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these targets were enriched in cell signaling and cancer-related pathways. Molecular docking confirmed that DEHP interacts with these core targets. DEHP may promote the development of BLCA by interacting with key proteins and signaling pathways. This study provides a theoretical basis for understanding the molecular mechanisms of DEHP-induced BLCA and offers references for future prevention and treatment strategies.

Diethylhexyl Phthalate↗
PubMed2026

Progesterone Is Associated With Increased Vasohibin-2 Expression, Tubulin Detyrosination, and Paclitaxel Sensitivity in PR-Negative Ovarian Cancer Cells.

BACKGROUND: Progesterone induces rapid cellular responses in progesterone receptor (PR)-negative ovarian cancer cells that are consistent with non-genomic progesterone signaling. Vasohibin-2 (VASH2), originally identified as a pro-angiogenic factor, has recently been recognized as a tubulin carboxypeptidase involved in microtubule regulation. AIMS: This study investigated the association of progesterone treatment with VASH2-related molecular changes and paclitaxel sensitivity in ovarian cancer cells. METHODS: Two PR-negative ovarian cancer cell lines expressing membrane progesterone receptors (mPRs) were treated with progesterone. VASH2 mRNA expression was evaluated by RT-qPCR, whereas detyrosinated tubulin and cyclin B1 expression were assessed by western blotting. Paclitaxel and gemcitabine sensitivities were determined using WST-1 cell viability assays. RESULTS: Progesterone treatment was associated with increased VASH2 mRNA expression, enhanced tubulin detyrosination, cyclin B1 accumulation, and significantly reduced paclitaxel IC50 values in both cell lines. In contrast, progesterone had no significant effect on gemcitabine sensitivity. CONCLUSION: Progesterone treatment was associated with increased VASH2 expression, enhanced tubulin detyrosination, and increased paclitaxel sensitivity in PR-negative ovarian cancer cells. These findings provide in vitro evidence supporting further mechanistic and preclinical investigation of progesterone as a potential adjunct to paclitaxel therapy.

Humans↗
PubMed2026

TRIM28 regulates the G2/M transition via histone modification and DNA damage repair during mouse oocyte meiosis.

TRIM28, a member of the tripartite motif (TRIM) family, functions as a transcriptional coregulator involved in maintaining genome stability during mitosis. In this study, we explored the role of TRIM28 in mouse oocyte meiotic maturation, where transcriptional activity is barely detectable. We found that TRIM28 was constitutively expressed during the early stages of oocyte meiotic maturation, with predominant nuclear localization in germinal vesicle (GV)-stage oocytes. TRIM28 depletion caused defective germinal vesicle breakdown (GVBD), but oocytes that successfully underwent GVBD displayed unimpaired first polar body (PB1) extrusion. TRIM28 depletion impaired CDK1 activity and reduced cyclin B1 levels, leading to a delay in the G2/M transition. This delay might be caused by altered levels of HDAC2-mediated H4K12ac and H3K4me2-modulated H3K9me2 in nonsurrounded nucleolus (NSN)-type GV oocytes, which decreased transcription activity. Additionally, TRIM28-depleted oocytes exhibited elevated γ-H2A.X expression, accompanied by aberrant expression of CHK1 and CHK2, as well as dysregulated expression of RAD51, which collectively contributed to GVBD failure in mouse oocytes. In conclusion, our findings indicate that TRIM28 participates in the regulation of the G2/M transition during mouse oocyte meiotic maturation, acting through the modulation of histone modifications and DNA damage repair.

Animals↗
PubMed2026

PDZ-binding kinase promotes ovarian cancer cell proliferation and invasion via CCNB1 regulation.

BACKGROUND: Ovarian cancer is one of the most lethal gynecological malignancies, characterized by late diagnosis, frequent recurrence, and high mortality. PDZ-binding kinase (PBK), a serine/threonine kinase of the mitogen-activated protein kinase kinase (MAPKK) family, has been implicated in the tumorigenesis of multiple cancers, yet its role in ovarian cancer remains incompletely characterized. This study aimed to investigate the effect of PBK on the proliferation and invasion of ovarian cancer cells. METHODS: The expression of PBK and cyclin B1 (CCNB1) in normal ovarian tissues and ovarian cancer tissues was analyzed using online databases including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Kaplan-Meier Plotter. Clinical tissue specimens were collected to detect the expression of PBK and CCNB1 by immunohistochemistry. Quantitative real-time polymerase chain reaction (PCR) was performed to detect PBK messenger RNA (mRNA) expression levels in clinical specimens and cell lines. Western blot was used to detect PBK protein expression in ovarian cancer cell lines. ES2 and A2780 cells with higher PBK expression were selected to construct PBK knockdown cell lines using lentiviral interference vectors. Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) assay were performed to explore the effect of PBK knockdown on cell proliferation. Transwell assay was used to investigate the effect on cell invasion. The Cancer Genome Atlas (TCGA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized to analyze PBK-related pathways and predict CCNB1 as the gene most closely related to PBK. RESULTS: PBK was significantly overexpressed in ovarian cancer tissues and cell lines compared with normal controls, and high PBK expression was associated with poor overall survival (OS) and progression-free survival (PFS). Knockdown of PBK expression inhibited the proliferation, colony formation, and invasion of ovarian cancer cells. Bioinformatics analysis revealed that CCNB1 was significantly overexpressed in ovarian cancer and high CCNB1 expression was associated with poor OS. CCNB1 was also significantly highly expressed in ovarian cancer tissues as validated by immunohistochemistry and was associated with lymph node metastasis. PBK and CCNB1 expression showed a significant positive correlation in TCGA ovarian cancer datasets. Knockdown of PBK inhibited CCNB1 expression in ovarian cancer cells. CONCLUSIONS: PBK promotes ovarian cancer cell proliferation and invasion. PBK knockdown leads to CCNB1 downregulation. These findings suggest that CCNB1 contributes to PBK-mediated oncogenic effects and identify the PBK-CCNB1 axis as a potential therapeutic target for ovarian cancer treatment.

PDZ-binding kinase (PBK)↗
PubMed2026

Developmental block in ruminant embryos: Mechanisms, molecular insights and potential interventions.

Developmental block remains one of the major hurdles that makes it hard to develop embryos in vitro more efficiently. In ruminants, it is predominantly observed during the 8-16 cell stage, coinciding with the maternal-to-zygotic transition (MZT) and embryonic genome activation (EGA). In addition, reducing maternal transcripts and initiating embryonic transcription correctly is a major reason for developmental arrest. A broad array of molecular mechanisms has been implicated, encompassing incomplete epigenetic regulation, mitochondrial dysfunction, oxidative stress, improper cell cycle progression, and dysregulated apoptosis. During this process, several key genes, including ZAR1, NPM2, DPPA3, DNMTs, Cyclin B1, BCL2, and antioxidant enzymes (SOD1, GPX1, and CAT) have been recognized as essential regulators of the block. External factors, especially poor in vitro culture conditions, high oxygen levels, and the secretion of harmful metabolites, make developmental failure even worse. Recent research has underscored the significance of antioxidant supplementation, epigenetic modulators, and enhanced culture systems in mitigating developmental barriers. Therefore, the current review summarises the contemporary insights into the factors and molecular mechanisms responsible for ruminant embryonic developmental block, focusing on MZT, oxidative stress, and epigenetic regulation. It also addresses potential strategies to enhance the developmental competence of ruminant embryos in vitro.

Embryo↗
PubMed2020

Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice.

Senescent cells accumulate with age in vertebrates and promote aging largely through their senescence-associated secretory phenotype (SASP). Many types of stress induce senescence, including genotoxic stress. ERCC1-XPF is a DNA repair endonuclease required for multiple DNA repair mechanisms that protect the nuclear genome. Humans or mice with reduced expression of this enzyme age rapidly due to increased levels of spontaneous, genotoxic stress. Here, we asked whether this corresponds to an increased level of senescent cells. p16Ink4a and p21Cip1 mRNA were increased ~15-fold in peripheral lymphocytes from 4- to 5-month-old Ercc1-/∆ and 2.5-year-old wild-type (WT) mice, suggesting that these animals exhibit a similar biological age. p16Ink4a and p21Cip1 mRNA were elevated in 10 of 13 tissues analyzed from 4- to 5-month-old Ercc1-/∆ mice, indicating where endogenous DNA damage drives senescence in vivo. Aged WT mice had similar increases of p16Ink4a and p21Cip1 mRNA in the same 10 tissues as the mutant mice. Senescence-associated β-galactosidase activity and p21Cip1 protein also were increased in tissues of the progeroid and aged mice, while Lamin B1 mRNA and protein levels were diminished. In Ercc1-/Δ mice with a p16Ink4a luciferase reporter, bioluminescence rose steadily with age, particularly in lung, thymus, and pancreas. These data illustrate where senescence occurs with natural and accelerated aging in mice and the relative extent of senescence among tissues. Interestingly, senescence was greater in male mice until the end of life. The similarities between Ercc1-/∆ and aged WT mice support the conclusion that the DNA repair-deficient mice accurately model the age-related accumulation of senescent cells, albeit six-times faster.

Aging↗