Serum/glucocorticoid-regulated kinase 1 contributes to the proliferation of varicella-zoster virus and induction of cyclin B1 expression.

In this study, we investigated the role of serum/glucocorticoid-regulated kinase 1 (SGK1) in varicella-zoster virus (VZV) replication. VZV DNA replication and plaque formation were inhibited by SGK1 knockout and treatment with an SGK1 inhibitor. Furthermore, SGK1 inhibition suppressed the increase in cyclin B1 expression induced by VZV infection. These results suggest that VZV infection induces SGK1 activation, which is required for efficient viral proliferation through the expression of cyclin B1. This is the first study to report that SGK1 is involved in the VZV life cycle.

KIF22 promotes multiple myeloma progression by regulating the CDC25C/CDK1/cyclinB1 pathway.

PURPOSE: Multiple myeloma (MM) is an incurable hematological malignancy characterized by clonal proliferation of malignant plasma B cells in bone marrow, and its pathogenesis remains unknown. The aim of this study was to determine the role of kinesin family member 22 (KIF22) in MM and elucidate its molecular mechanism. METHODS: The expression of KIF22 was detected in MM patients based upon the public datasets and clinical samples. Then, in vitro assays were performed to investigate the biological function of KIF22 in MM cell lines, and subcutaneous xenograft models in nude mice were conducted in vivo. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay were used to determine the mechanism of KIF22-mediated regulation. RESULTS: The results demonstrated that the expression of KIF22 in MM patients was associated with several clinical features, including gender (P = 0.016), LDH (P < 0.001), ß2-MG (P = 0.003), percentage of tumor cells (BM) (P = 0.002) and poor prognosis (P < 0.0001). Furthermore, changing the expression of KIF22 mainly influenced the cell proliferation in vitro and tumor growth in vivo, and caused G2/M phase cell cycle dysfunction. Mechanically, KIF22 directly transcriptionally regulated cell division cycle 25C (CDC25C) by binding its promoter and indirectly influenced CDC25C expression by regulating the ERK pathway. KIF22 also regulated CDC25C/CDK1/cyclinB1 pathway. CONCLUSION: KIF22 could promote cell proliferation and cell cycle progression by transcriptionally regulating CDC25C and its downstream CDC25C/CDK1/cyclinB1 pathway to facilitate MM progression, which might be a potential therapeutic target in MM.

[Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses].

OBJECTIVE: To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. METHODS: High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. RESULTS: Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5- and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. CONCLUSION: TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Regulatory Role of Meox1 in Muscle Growth of Sebastes schlegelii.

Meox1 is a critical transcription factor that plays a pivotal role in embryogenesis and muscle development. It has been established as a marker gene for growth-specific muscle stem cells in zebrafish. In this study, we identified the SsMeox1 gene in a large teleost fish, Sebastes schlegelii. Through in situ hybridization and histological analysis, we discovered that SsMeox1 can be employed as a specific marker of growth-specific muscle stem cells, which originate from the somite stage and are primarily situated in the external cell layer (ECL) and myosepta, with a minor population distributed among muscle fibers. The knockdown of SsMeox1 resulted in a significant increase in Ccnb1 expression, subsequently promoting cell cycle progression and potentially accelerating the depletion of the stem cell pool, which ultimately led to significant growth retardation. These findings suggest that SsMeox1 arrests the cell cycle of growth-specific muscle stem cells in the G2 phase by suppressing Ccnb1 expression, which is essential for maintaining the stability of the growth-specific muscle stem cell pool. Our study provides significant insights into the molecular mechanisms underlying the indeterminate growth of large teleosts.

Effects of silencing NLRP3 gene on proliferation of psoriasis-like HaCaT cells and expressions of cytokines.

We aimed to explore the effects of silencing NOD-like receptor protein 3 (NLRP3) on proliferation of psoriasis-like HaCaT cells and expressions of cytokines. HaCaT cells were treated with human keratinocyte growth factor (KGF) and were divided into KGF group, negative control group, NLRP3-RNAi group and control group. Cells proliferation was detected by CCK8, cell clone formation rate was detected by clone formation assay, distribution of cells cycle was detected by flow cytometry, expressions of cyclin B1 (Cyclin B1), cyclin-dependent kinase 2 (CDK2), Ki67 and proliferating cell nuclear antigen (PCNA) proteins were detected by Western blot, and levels of interleukin (IL)-17, IL-23, IL-6 and tumor necrosis factor α (TNF-α) were detected by enzyme-linked immunosorbent assay. Compared with control group, expressions of NLRP3 mRNA and protein, proliferation rate and clonal formation rate were increased in KGF group, percentage of cells in G0/G1 phase was decreased, percentage of cells in S phase was increased, expressions of Cyclin B1, CDK2, Ki67 and PCNA proteins were increased, and levels of IL-17, IL-23, IL-6 and TNF-α were increased. Compared with negative control group, expressions of NLRP3 mRNA and protein, proliferation rate and clonal formation rate were decreased in NLRP3-RNAi group, percentage of cells in G0/G1 phase was increased, percentage of cells in S phase was decreased, expressions of Cyclin B1, CDK2, Ki67 and PCNA proteins were decreased, and levels of IL-17, IL-23, IL-6 and TNF-α were decreased. Silencing NLRP3 gene can inhibit the proliferation of psoriasis-like HaCaT cells, arrest cell cycle, inhibit the expressions of cell proliferation-related proteins and reduce levels of pro-inflammatory factors.

Toxoplasma gondii modulates the host cell cycle, chromosome segregation, and cytokinesis irrespective of cell type or species origin.

BACKGROUND: Toxoplasma gondii is an apicomplexan intracellular obligate parasite and the etiological agent of toxoplasmosis in humans, domestic animals and wildlife, causing miscarriages and negatively impacting offspring. During its intracellular development, it relies on nutrients from the host cell, controlling several pathways and the cytoskeleton. T. gondii has been proven to control the host cell cycle, mitosis and cytokinesis, depending on the time of infection and the origin of the host cell. However, no data from parallel infection studies have been collected. Given that T. gondii can infect virtually any nucleated cell, including those of humans and animals, understanding the mechanism by which it infects or develops inside the host cell is essential for disease prevention. Therefore, we aimed here to reveal whether this modulation is dependent on a specific cell type or host cell species. METHODS: We used only primary cells from humans and bovines at a maximum of four passages to ensure that all cells were counted with appropriate cell cycle checkpoint control. The cell cycle progression was analysed using fluorescence-activated cell sorting (FACS)-based DNA quantification, and its regulation was followed by the quantification of cyclin B1 (mitosis checkpoint protein). The results demonstrated that all studied host cells except bovine colonic epithelial cells (BCEC) were arrested in the S-phase, and none of them were affected in cyclin B1 expression. Additionally, we used an immunofluorescence assay to track mitosis and cytokinesis in uninfected and T. gondii-infected cells. RESULTS: The results demonstrated that all studied host cell except bovine colonic epithelial cells (BCEC) were arrested in the S-phase, and none of them were affected in cyclin B1 expression. Our findings showed that the analysed cells developed chromosome segregation problems and failed to complete cytokinesis. Also, the number of centrosomes per mitotic pole was increased after infection in all cell types. Therefore, our data suggest that T. gondii modulates the host cell cycle, chromosome segregation and cytokinesis during infection or development regardless of the host cell origin or type.

Naringenin nanoparticles targeting cyclin B1 suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition.

There is growing evidence of an elevated risk of lung cancer in patients with rheumatoid arthritis. The poor prognosis of rheumatoid arthritis-associated lung cancer and the lack of therapeutic options pose an even greater challenge to the clinical management of patients. This study aimed to identify potential molecular targets associated with the progression of rheumatoid arthritis-associated lung cancer and examine the efficacy of naringenin nanoparticles targeting cyclin B1. Mendelian randomizatio analysis revealed that rheumatoid arthritis has a positive correlation with the risk of lung cancer. Cyclin B1 was significantly upregulated in patients with rheumatoid arthritis-associated lung cancer and was significantly overexpressed in synovial tissue fibroblasts. Furthermore, the overexpression of cyclin B1 in rheumatoid arthritis fibroblast-like synoviocytes, which promotes their proliferation and fibroblast-to-myofibroblast transition, can significantly contribute to the growth and infiltration of lung cancer cells. Importantly, our prepared naringenin nanoparticles targeting cyclin B1 effectively attenuated proliferation and fibroblast-to-myofibroblast transition by blocking cells at the G2/M phase. In vivo experiments, naringenin nanoparticles targeting cyclin B1 significantly alleviated the development of collagen-induced arthritis and lung orthotopic tumors. Collectively, our results reveal that naringenin nanoparticles targeting cyclin B1 can suppress the progression of rheumatoid arthritis-associated lung cancer by inhibiting fibroblast-to-myofibroblast transition. These findings provide new insights into the treatment of rheumatoid arthritis-associated lung cancer therapy.

Bioinformatics analysis highlights CCNB1 as a potential prognostic biomarker and an anti-kidney renal papillary cell carcinoma drug target.

Kidney renal papillary cell carcinoma (KIRP) is a common urinary tumor that causes lymph node invasion. Once metastatic, the prognosis is poor and there is a lack of effective early diagnostic markers for this tumor. The expression of CCNB1 in KIRP tumor tissues was significantly higher than that in normal tissues in The Cancer Genome Atlas database with or without the genotype-tissue expression database, and a consistent result was obtained in 32 paired tissues. In addition, CCNB1 expression increased remarkably with the progression of the T and M stages. Moreover, using the online HPA database, we verified that the immunohistochemical scores of CCNB1 in KIRP were higher than those in the normal kidney tissues. The higher expression group of CCNB1 showed a worse prognosis in KIRP. Moreover, the receiver operating characteristic curve, univariate and multivariate analyses, and construction of the column diagram further illustrated that CCNB1 was an independent prognostic factor for KIRP. Meanwhile, CCNB1 could better predict the 1- and 3-year survival rates of KIRP. Six genes were significantly and positively co-expressed with CCNB1. We also found that the CCNB1 high-expression group was enriched in the ECM_RECEPTOR_INTERACTION and FOCAL_ADHESION pathways. Finally, drug sensitivity analysis combined with molecular docking identified 5 targeting drugs with the strongest binding activity to CCNB1. CCNB1 is a potential and reliable biomarker for KIRP diagnosis and can be used to predict the survival of patients with KIRP. The 5 selected drugs targeting CCNB1 may provide new hopes for patients with KIRP metastasis.

BRCA1 deficiency enhances the aggressiveness of breast cancer cells expressing HPV16 oncoproteins.

BACKGROUND INFORMATION: The precise etiology of breast cancer is not completely understood, although women with BRCA1 gene mutations have a significantly increased risk of developing the disease. In addition, sporadic breast cancer is frequently associated with decreased BRCA1 gene expression. Growing evidence of Human papillomaviruses (HPVs) infections in breast tumors has raised the possibility of the involvement of HPVs in the pathogenesis of breast cancer. We investigated whether the effects of HPV oncoproteins E6 and E7 were influenced by the expression levels of BRCA1. HPV16E6E7 (prototype or E6D25E/E7N29S Asian variant type) were stably expressed in MDA-MB231 breast cancer cells, wild type for BRCA1, or with BRCA1 knocked down. RESULTS: Expression of HPV16E6E7 oncogenes did not affect BRCA1 levels and the abundance of HPV16E6E7 was not altered by BRCA1 knockdown. BRCA1 levels did not alter HPV16E6E7-dependent degradation of G1-S cell cycle proteins p53 and pRb. However, we found that the expression of G2-M cell cycle protein cyclin B1 enhanced by HPV16E6E7 was impacted by BRCA1 levels. Especially, we found the correlation between BRCA1 and cyclin B1 expression and this was also confirmed in breast cancer samples from a Thai cohort. We further demonstrated that the combination of HPV oncoproteins and low levels of BRCA1 protein appears to enhance proliferation and invasion. Transactivation activities of HPV16E6E7 on genes regulating cell proliferation and invasion (TGF-ß and vimentin) were significantly increased in BRCA1-deficient cells. CONCLUSIONS: Our results indicate that a deficiency of BRCA1 promotes the transactivation activity of HPV16E6E7 leading to increase of cell proliferation and invasion. SIGNIFICANCE: HPV infection appears to have the potential to enhance the aggressiveness of breast cancers, especially those deficient in BRCA1.

Unraveling the interplay between PKA inhibition and Cdk1 activation during oocyte meiotic maturation.

Oocytes are arrested in prophase I. In vertebrates, meiotic resumption is triggered by hormonal stimulation that results in cAMP-dependent protein kinase (PKA) downregulation leading to Cdk1 activation. Yet the pathways connecting PKA to Cdk1 remain unclear. Here, we identify molecular events triggered by PKA downregulation occurring upstream of Cdk1 activation. We describe a two-step regulation controlling cyclin B1 and Mos accumulation, which depends on both translation and stabilization. Cyclin B1 accumulation is triggered by PKA inhibition upstream of Cdk1 activation, while its translation requires Cdk1 activity. Conversely, Mos translation initiates in response to the hormone, but the protein accumulates only downstream of Cdk1. Furthermore, two successive translation waves take place, the first controlled by PKA inhibition and the second by Cdk1 activation. Notably, Arpp19, an essential PKA effector, does not regulate the early PKA-dependent events. This study elucidates how PKA downregulation orchestrates multiple pathways that converge toward Cdk1 activation and induce the oocyte G2/M transition.

Сopper nanoparticles supported on charcoal and betacellulin - Two novel stimulators of ovarian granulosa cell functions and their functional interrelationships.

The present experiments are aimed to examine the effect of copper nanoparticles supported on charcoal (CuNPs/C), growth factor betacellulin (BTC) and their interrelationships in the control of ovarian cell functions. Porcine ovarian granulosa cells were cultured in the presence of CuNPs/C (0, 1, 10 or 100 ng/ml), BTC (100 ng/ml) and the combination of both, CuNPs/C + BTC. Markers of cell proliferation (BrDU incorporation), of the S-phase (PCNA) and G-phase (cyclin B1) of the cell cycle, markers of extrinsic (nuclear DNA fragmentation) and cytoplasmic/mitochondrial apoptosis (bax and caspase 3), and the release of progesterone and estradiol were assessed by BrDU test, TUNEL, quantitative immunocytochemistry and ELISA. Both CuNPs/C and BTC, when added alone, increased the expression of all the markers of cell proliferation, reduced the expression of all apoptosis markers and stimulated progesterone and estradiol release. Moreover, BTC was able to promote the CuNPs/C action on the accumulation of PCNA, cyclin B1, bax and estradiol output. These observations demonstrate the stimulatory action of both CuNPs/C and BTC on ovarian cell functions, as well as the ability of BTC to promote the action of CuNPs/C on ovarian cell functions.

Kielin/chordin-like protein deficiency aggravates pressure overload-induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice.

Targeting cardiac remodeling is regarded as a key therapeutic strategy for heart failure. Kielin/chordin-like protein (KCP) is a secretory protein with 18 cysteine-rich domains and associated with kidney and liver fibrosis. However, the relationship between KCP and cardiac remodeling remains unclear. Here, we aimed to investigate the role of KCP in cardiac remodeling induced by pressure overload and explore its potential mechanisms. Left ventricular (LV) KCP expression was measured with real-time quantitative PCR, western blotting, and immunofluorescence staining in pressure overload-induced cardiac remodeling in mice. Cardiac function and remodeling were evaluated in wide-type (WT) mice and KCP knockout (KO) mice by echocardiography, which were further confirmed by histological analysis with hematoxylin and eosin and Masson staining. RNA sequence was performed with LV tissue from WT and KO mice to identify differentially expressed genes and related signaling pathways. Primary cardiac fibroblasts (CFs) were used to validate the regulatory role and potential mechanisms of KCP during fibrosis. KCP was down-regulated in the progression of cardiac remodeling induced by pressure overload, and was mainly expressed in fibroblasts. KCP deficiency significantly aggravated pressure overload-induced cardiac dysfunction and remodeling. RNA sequence revealed that the role of KCP deficiency in cardiac remodeling was associated with cell division, cell cycle, and P53 signaling pathway, while cyclin B1 (CCNB1) was the most significantly up-regulated gene. Further investigation in vivo and in vitro suggested that KCP deficiency promoted the proliferation of CFs via P53/P21/CCNB1 pathway. Taken together, these results suggested that KCP deficiency aggravates cardiac dysfunction and remodeling induced by pressure overload via P53/P21/CCNB1 signaling in mice.

Inhibition of vinculin activity has an adverse effect on porcine ovarian cells.

The existing knowledge of the involvement of vinculin (VCL) in the control of ovarian cell functions is insufficient. To understand the role of VCL in the control of basic porcine ovarian granulosa cell functions, we decreased VCL activity by small interfering RNA (VCL siRNA). The expression of VCL, accumulation of VCL protein, cell viability, proliferation (accumulation of PCNA and cyclin B1), proportion of proliferative active cells, apoptosis (accumulation of bax, caspase 3, p53, antiapoptotic marker bcl2, and bax/bcl-2 ratio), DNA fragmentation, and release of steroid hormones and IGF-I were analyzed by RT‒qPCR, Trypan blue exclusion test, quantitative immunocytochemistry, XTT assay, TUNEL assay, and ELISA. The suppression of VCL activity inhibited cell viability, the accumulation of the proliferation-related proteins PCNA and cyclin B1, the antiapoptotic protein bcl2, and the proportion of proliferative active cells. Moreover, VCL siRNA inhibited the release of progesterone, estradiol, and IGF-1. VCL siRNA increased the proportion of the proapoptotic proteins bax, caspase 3, p53, the proportion of DNA fragmented cells, and stimulated testosterone release. Taken together, the present study is the first evidence that inhibition of VCL suppresses porcine granulosa cell functions. Moreover, the results suggest that VCL can be a potent physiological stimulator of ovarian functions.

Prognostic value of cyclin B1 and cyclin B2 expression in breast cancer: A systematic review and updated meta-analysis.

BACKGROUND: Cyclin B1 and cyclin B2 are key regulators of cell cycle progression and have been implicated in the prognostic significance of various cancers. This meta-analysis aimed to evaluate the prognostic value of cyclin B1 and B2 expression in breast cancer. METHODS: A comprehensive literature search was conducted on Pubmed, Embase, MEDLINE, Web of Science, and Cochrane library. Studies with survival data and clinicopathological parameters associated with cyclin B1 and B2 or CCNB1 and CCNB2 genes were included. Survival data and clinicopathological parameters associated with cyclin B1 and B2 expression were extracted. Pooled hazard ratios and odds ratios with 95% confidence intervals were calculated. Subgroup analysis was conducted to assess heterogeneity. Publication bias was evaluated. RESULTS: A total of 23 studies were included in the analysis. High expression of cyclin B1 was significantly associated with worse overall survival (hazard ratio [HR] = 1.69, P < .01), disease-specific survival (HR = 1.71, P < .01), and disease-free survival (HR = 2.01, P = .01). High expression of cyclin B2 was associated with worse disease-specific survival (HR = 2.46, P = .02). Clinicopathological parameters did not show significant associations with cyclin B1 and B2 expressions. When data on cyclin B1 and B2 were combined, a significant age-related difference was found (odds ratio = 0.62, P = .04). CONCLUSIONS: This meta-analysis provides evidence supporting the prognostic significance of cyclin B1 and B2 expression in breast cancer. High expression of cyclin B1 and B2 is associated with worse survival, indicating their potential as prognostic markers in breast cancer.

CDCA8 Facilitates Tumor Proliferation and Predicts a Poor Prognosis in Hepatocellular Carcinoma.

CDCA8 expression is abnormally high in a variety of cancers and involved in the biological process of tumor malignancy. In this study, we discovered that the expression of CDCA8 was up-regulated in hepatocellular carcinoma cancer (HCC) tissues and high levels of CDCA8 are associated with larger tumor size, higher AFP (α-fetoprotein) levels, and unfavorable prognosis. Cell functional experiments revealed that CDCA8 silencing remarkably inhibited proliferation and promoted apoptosis in SNU-387 and Hep-3B cells. The results of flow cytometry showed that CDCA8 regulated CDK1 and cyclin B1 expression to arrest at the S phase, inhibited proliferation, and promoted apoptosis. In addition, in vivo studies have confirmed that silencing CDCA8 could regulate CDK1/cyclin B1 signaling axis to inhibit the growth of HCC xenograft tumor. Our study demonstrated CDCA8 acts an oncogene to facilitate cell proliferation of HCC via regulating cell cycle, indicating the promising application value of CDCA8 for HCC diagnosis and clinical treatment.

Alternative cleavage and polyadenylation of the Ccnb1 mRNA defines accumulation of cyclin protein during the meiotic cell cycle.

Progression through the mitotic and meiotic cell cycle is driven by fluctuations in the levels of cyclins, the regulatory subunits controlling the localization and activity of CDK1 kinases. Cyclin levels are regulated through a precise balance of synthesis and degradation. Here we demonstrate that the synthesis of Cyclin B1 during the oocyte meiotic cell cycle is defined by the selective translation of mRNA variants generated through alternative cleavage and polyadenylation (APA). Using gene editing in mice, we introduced mutations into the proximal and distal polyadenylation elements of the 3' untranslated region (UTR) of the Ccnb1 mRNA. Through in vivo loss-of-function experiments, we demonstrate that the translation of mRNA with a short 3' UTR specifies Cyclin B1 protein levels that set the timing of meiotic re-entry. In contrast, translation directed by a long 3' UTR is necessary to direct Cyclin B1 protein accumulation during the MI/MII transition. These findings establish that the progression through the cell cycle is dependent on the selective translation of multiple mRNA variants generated by APA.

BubR1 and cyclin B1 immunoexpression in pleomorphic adenoma and polymorphous adenocarcinoma of minor salivary glands.

The immunoexpression of BubR1 and cyclin B1 in pleomorphic adenoma (PA) and polymorphic adenocarcinoma (PAC) in minor salivary glands is poorly studied. Thus, a retrospective and observational study was performed to provide a better understanding of the role and immunopositivity patterns of these proteins in these lesions. Sixteen cases of PA and 16 cases of PAC were selected. Parenchyma cells were submitted to quantitative immunohistochemical analysis through the labeling index. Cytoplasmic immunoexpression of BubR1 was observed in neoplastic cells from all analyzed PA and PAC cases. All PA cases and 93.7% of PAC exhibited nuclear immunoexpression of BubR1. Higher cytoplasmic and nuclear immunoexpression of BubR1 was observed in PAC (p = 0.001 and p = 0.122, respectively). Cytoplasmic immunoexpression of cyclin B1 was observed in all cases of PA and PAC, with a higher labeling index in the latter (p < 0.001). There was a significant positive correlation between nuclear and cytoplasmic BubR1 immunoexpressions (p < 0.001) in PA and a significant negative correlation between BubR1 and cyclin B1 cytoplasmic immunoexpressions (p = 0.014) in PAC. The higher cytoplasmic and nuclear immunoexpression of BubR1 in PACs suggests the continuous maintenance of neoplastic cells in the cell cycle and migration. Higher immunoexpression of cyclin B1 supports this lesion's enhanced proliferative and migration ability.

DEPDC1B enhances malignant phenotypes of multiple myeloma through upregulating CCNB1 and inhibiting p53 signaling pathway.

The identification and investigation of key molecules involved in the pathogenesis of multiple myeloma (MM) hold paramount clinical significance. This study primarily focuses on elucidating the role of DEPDC1B within the context of MM. Our findings robustly affirm the abundant expression of DEPDC1B in MM tissues and cell lines. Notably, DEPDC1B depletion exerted inhibitory effects on MM cell proliferation and migration while concurrently facilitating apoptosis and G2 cell cycle arrest. These outcomes stand in stark contrast to the consequences of DEPDC1B overexpression. Furthermore, we identified CCNB1 as a putative downstream target, characterized by a co-expression pattern with DEPDC1B, mediating DEPDC1B's regulatory influence on MM. Additionally, our results suggest that DEPDC1B knockdown may activate the p53 pathway, thereby impeding MM progression. To corroborate these in vitro findings, we conducted in vivo experiments that further validate the regulatory role of DEPDC1B in MM and its interaction with CCNB1 and the p53 pathway. Collectively, our research underscores DEPDC1B as a potent promoter in the development of MM, representing a promising therapeutic target for MM treatment. This discovery bears significant implications for future investigations in this field.

SETDB2 interacts with BUBR1 to induce accurate chromosome segregation independently of its histone methyltransferase activity.

SETDB2 is a H3K9 histone methyltransferase required for accurate chromosome segregation. Its H3K9 histone methyltransferase activity was reported to be associated with chromosomes during metaphase. Here, we confirm that SETDB2 is required for mitosis and accurate chromosome segregation. However, these functions are independent of its histone methyltransferase activity. Further analysis showed that SETDB2 can interact with BUBR1, and is required for CDC20 binding to BUBR1 and APC/C complex and CYCLIN B1 degradation. The ability of SETDB2 to regulate the binding of CDC20 to BUBR1 or APC/C complex, and stabilization of CYCLIN B1 are also independent of its histone methyltransferase activity. These results suggest that SETDB2 interacts with BUBR1 to promote binding of CDC20 to BUBR1 and APC3, then degrades CYCLIN B1 to ensure accurate chromosome segregation and mitosis, independently of its histone methyltransferase activity.

Resveratrol affects ccRCC cell senescence and macrophage polarization by regulating the stability of CCNB1 by RBM15.

Aim: The present study sought to investigate the therapeutic effect of resveratrol on clear cell renal cell carcinoma. Materials & methods: Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to verify the cell proliferation. Transwell, real-time quantitative transcription PCR, western blot and ß-galactosidase staining were used to verify the migration, macrophage polarization and senescence. The tumor inhibitory effect of resveratrol on clear cell renal cell carcinoma was verified in vivo. Results: This study confirmed that resveratrol could affect the stability of CCNB1 mRNA mediated by RBM15 and inhibit the cancer process by inhibiting the expression of EP300/CBP from the perspective of cell senescence. Conclusion: Resveratrol is able to treat clear cell renal cell carcinoma through RBM15-induced cell senescence.