The centrosome is the microtubule-organizing center and a crucial part of cell division.Centrosomal RNAs(cnRNAs)have been reported to enable precise spatiotemporal control of gene expression during cell division in ma...The centrosome is the microtubule-organizing center and a crucial part of cell division.Centrosomal RNAs(cnRNAs)have been reported to enable precise spatiotemporal control of gene expression during cell division in many species.Whether and how cnRNAs exist in C.elegans are unclear.Here,using the nuclear RNAi Argonaute protein NRDE-3 as a reporter,we observed potential peri-centrosome localized small interfering(si)RNAs in C.elegans.NRDE-3 was previously shown to associate with pre-mRNAs and pre-rRNAs via a process involving the presence of complementary siRNAs.We generated a GFP-NRDE-3 knock-in transgene through CRISPR/Cas9 technology and observed that NRDE-3 formed peri-centrosomal foci neighboring the tubulin protein TBB-2,other centriole proteins and pericentriolar material(PCM)components in C.elegans embryos.The peri-centrosomal accumulation of NRDE-3 depends on RNA-dependent RNA polymerase(RdRP)-synthesized 22G siRNAs and the PAZ domain of NRDE-3,which is essential for siRNA binding.Mutation of eri-1,ergo-1,or drh-3 significantly increased the percentage of pericentrosome-enriched NRDE-3.At the metaphase of the cell cycle,NRDE-3 was enriched in both the peri-centrosomal region and the spindle.Moreover,the integrity of centriole proteins and pericentriolar material(PCM)components is also required for the peri-centrosomal accumulation of NRDE-3.Therefore,we concluded that siRNAs could accumulate in the pericentrosomal region in C.elegans and suggested that the peri-centrosomal region may also be a platform for RNAi-mediated gene regulation.展开更多
Cenpj is a centrosomal protein located at the centrosomes and the base of cilia,it plays essential roles in regulating neurogenesis and cerebral cortex development.Although centrosomal and cilium dysfunction are one o...Cenpj is a centrosomal protein located at the centrosomes and the base of cilia,it plays essential roles in regulating neurogenesis and cerebral cortex development.Although centrosomal and cilium dysfunction are one of the causes of obesity,insulin resistance,and type 2 diabetes,the role that Cenpj plays in the regulation of body weight remains unclear.Here,we deleted Cenpj by crossing Cenpjflox/flox mice with Nkx2.1-Cre mice.Loss of the centrosomal protein Cenpj in Nkx2.1-expressing cells causes morbid obesity in mice at approximately 4 months of age with expended brain ventricles but no change of brain size.We found that hypothalamic cells exhibited reduced proliferation and increased apoptosis upon Cenpj depletion at the embryonic stages,resulting in a dramatic decrease in the number of Proopiomelanocortin(POMC)neurons and electrophysiological dysfunction of NPY neurons in the arcuate nucleus(ARC)in adults.Furthermore,depletion of Cenpj also reduced the neuronal projection from the ARC to the paraventricular nucleus(PVN),with decreased melanocortin-4 receptors(MC4R)expression in PVN neurons.The study defines the roles that Cenpj plays in regulating hypothalamus development and body weight,providing a foundation for further understanding of the pathological mechanisms of related diseases.展开更多
Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 k...Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.展开更多
The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKS...The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.展开更多
Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells...Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells.This makes the centrosome a promising target for therapeutic strategies in cancer treatment.Methods:Utilizing data from the TCGA database,we identified centrosome-related genes and constructed a prognostic model for 518 lung adenocarcinoma patients.Prognosis-associated genes were initially screened using univariate Cox regression,with overfitting minimized by applying LASSO regression to remove collinearity.Finally,a set of 12 genes was selected through multivariable Cox regression for inclusion in the prognostic model.Results:The model’s performance was assessed using ROC curve analysis,demonstrating a robust predictive ability with an AUC of 0.728 in the training group and 0.695 in the validation group.Differential expression analysis between high-risk(HRLAs)and low-risk(LRLAs)individuals was performed,followed by enrichment analyses using KEGG,GO,Progeny,GSVA,and GSEA.These analyses revealed significant differences in immune-related pathways between the two groups.Immune microenvironment assessment through ssGSEA and ESTIMATE indicated that individuals with poor prognosis exhibited lower immune,stromal,and ESTIMATE scores,along with higher tumor purity,suggesting an impaired immune microenvironment in HRLAs patients.Drug susceptibility analysis and molecular docking showed that HRLAs individuals were more responsive to docetaxel,emphasizing the therapeutic relevance of paclitaxel in this cohort.Conclusion:We successfully developed and validated a centrosome-associated gene-based prognostic model,offering clinicians valuable insights for improved decision-making and personalized treatment strategies.This model may facilitate the identification of high-risk patients and guide therapeutic interventions in lung adenocarcinoma.展开更多
OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the bre...OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.展开更多
To explore the relationship between STK15 gene abnormal expression and laryngeal carcinoma. Methods: Tumor tissues and matched normal tissues were taken from 55 LSCC patients. Semi-quantitative reverse transcription-p...To explore the relationship between STK15 gene abnormal expression and laryngeal carcinoma. Methods: Tumor tissues and matched normal tissues were taken from 55 LSCC patients. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect STK15 expression in 110 specimens. Results: In 38 of the 55 cases (69.1%), the STK15 expression at the mRNA levels was higher than that of the paired normal tissue. The ratio of ADV (average density value) of STK15 gene to ADV of b-actin gene was 1.220.49 in the cancer tissue, and 0.990.54 in the paired normal tissue with a significant difference (t=4.539, P<0.01). Conclusion: There was obvious association between the STK15 overexpression and laryngeal carcinoma. It may serve as an alternative mechanism of activating the pathogenesis of human laryngeal squamous cell carcinoma.展开更多
Colon cancer is currently the third most common cancer and second most fatal cancer in the United States,resulting in approximately 600,000 deaths annually.Though colorectal cancer death rates are decreasing by about ...Colon cancer is currently the third most common cancer and second most fatal cancer in the United States,resulting in approximately 600,000 deaths annually.Though colorectal cancer death rates are decreasing by about 3%every year,disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis,the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments.Colon carcinogenesis is notably a slow process that can take decades.Known factors that contribute to the development of colon cancer are mutational,epigenetic and environmental,and risk factors include age,history of polyps and family history of colon cancer.Colorectal cancers exhibit heterogeneity in their features and are often characterized by the presence of chromosomal instability,microscopic satellite instability,or CpG island methylator phenotype.In this review,we propose that centrosome amplification may be a widespread occurrence in colorectal cancers and could potently influence tumor biology.Moreover,the quantitation of this cancer-specific anomaly could offer valuable prognostic information and pave the way for further customization of treatment based on the organellar profile of patients.Patient stratification models that take into account centrosomal status could thus potentially reduce adverse side effects and result in improved outcomes for colorectal cancer patients.展开更多
The objective herein was to connect the ontogeny process of diplochromosomal, amitotic, 4n-skewed division-system, to cytogenetic deficiency lesions in satellite, repetitive DNAs, especially in the chromosomal fragile...The objective herein was to connect the ontogeny process of diplochromosomal, amitotic, 4n-skewed division-system, to cytogenetic deficiency lesions in satellite, repetitive DNAs, especially in the chromosomal fragile sites, some 100 distributed over the genome. These latter studies had shown that chemical induced replication-stress led to un-replicated lesions in these fragile sites, which from inaccurate repair processes caused genomic instability. In the chain of events of the ontogeny process to the special tetraploidy, it was proposed that primary damaged human cells could undergo replication stress from repair-process present during cell replication, a suggestion verified by X-ray damaged cells producing the unstable fragile sites (see text). The cancer-importance for therapy is recognition of cell cycle change for the 4n derivative fitness-gained, diploid progeny cells. An open question is whether RB controlling G1 to S-period is mutated at this suggested tumorigenesis initiating phase, and if so, with what consequences for therapy. The fragile site studies further showed that repair of repetitive DNAs could produce two types of genomic changes: single gene mutations and CNVs, which were here shown to be chromosomally located on “borders” to repairing satellite lesions. This genomic placement was found to correspond to mutations identified in tumor sequencing (p53, Rb, MYC), favoring a bad luck location for their cancer “mutational nature”. The CNVs in cancers, are here seen as molecular expressions of long-known cytogenetic HSRs and DMs also with demonstrated origin from amplifications of single genes. Over-expression of oncogenes was hinted of being from duplications, but Drosophila genetics demonstrated the opposite, gene inactivation. The reduced eye-size from dominant, BAR-Ultra-Bar-eye phenotypes, was caused by duplications, inactivating the genetic system for eye-size. The finding of CNVs showing “evasion” of the immune system suggests, inactivation of immune-determining genetics. Since mutated genes on borders to satellite DNAs are a fact in hematological cancers, the 4n-skewed division-system is suggested to replace debated leukemogenesis with fitness-gain from molecular mutations. For these cancers the question is how normal bone marrow cells attain genomic damage for special tetraploidy, which was referred to studies of cells moving in artificial marrow-like substrate, needing serious attention.展开更多
Sperm are a highly specialized cell type derived to deliver the paternal haploid genome to the oocyte. The epigenetic, or gene regulatory, properties and mechanisms of the sperm assist in preparation of the paternal g...Sperm are a highly specialized cell type derived to deliver the paternal haploid genome to the oocyte. The epigenetic, or gene regulatory, properties and mechanisms of the sperm assist in preparation of the paternal genome to contribute to embryogenesis and the genome of the zygote. Many recent studies have addressed the issue of altered epigenetic processes in the sperm. This review evaluates the current understanding of DNA damage, chromosome aneuploidy, reduced telomere length, malformations of the centrosome, genomic imprinting errors, altered mRNA profiles, and abnormal nuclear packaging in the sperm prior to fertilization and the observed effects on embryogenesis. Attention has also been given to understanding the underlying etiology of sperm with altered epigenetic mechanisms in humans. （Asian J Androl 2006 Mar; 8： 131-142）展开更多
Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length,pole formation,and known for clustering extra centrosomes in cancer cells.Centrosome clustering is associated with the survival of...Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length,pole formation,and known for clustering extra centrosomes in cancer cells.Centrosome clustering is associated with the survival of cancer cells,but this phenomenon remains obscure in prostate cancer(PCa).The present study demonstrated that PCa cells showed centrosome amplification and clustering during interphase and mitosis,respectively.KIFC1 is highly expressed in PCa cells and tumor tissues of prostatic adenocarcinoma(PAC)patients.Up-regulation of KIFC1 facilitated the PCa cell survival in vitro by ensuring bipolar mitosis through clustering the multiple centrosomes,suggesting centrosome clustering could be a leading cause of prostate carcinogenesis.Conversely,the silencing of KIFC1 resulted in normal centrosome number or multipolar mitosis by inhibiting the clustering of amplified centrosomes in PCa cells.Besides,knockdown of KIFC1 by RNAi in PCa cells reduced cancer cell survival,and proliferation.KIFC1 interacted with centrosome structural protein Centrin 2 in clustering of amplified centrosomes in PCa cells to ensure the bipolar mitotic spindle formation.Knockdown of Centrin 2 in PCa cells inhibited the centrosome amplification and clustering.Moreover,up-regulated KIFC1 promotes PCa cell proliferation via progression of cell cycle possibly through aberrant activation of cyclin dependent kinase 1(Cdk1).Therefore,KIFC1 can be a prognostic marker and therapeutic target of PCa for inhibiting the cancer cell proliferation.展开更多
At the core of regenerative medicine lies the expectation of repair or replacementof damaged tissues or whole organs. Donor scarcity and transplant rejection aremajor obstacles, and exactly the obstacles that stem cel...At the core of regenerative medicine lies the expectation of repair or replacementof damaged tissues or whole organs. Donor scarcity and transplant rejection aremajor obstacles, and exactly the obstacles that stem cellbased therapy promisesto overcome. These therapies demand a comprehensive understanding of theasymmetric division of stem cells, i.e. their ability to produce cells with identicalpotency or differentiated cells. It is believed that with better understanding,researchers will be able to direct stem cell differentiation. Here, we describeextraordinary advances in manipulating stem cell fate that show that we need tofocus on the centrosome and the centrosome-derived primary cilium. This beliefcomes from the fact that this organelle is the vehicle that coordinates theasymmetric division of stem cells. This is supported by studies that report thesignificant role of the centrosome/cilium in orchestrating signaling pathways thatdictate stem cell fate. We anticipate that there is sufficient evidence to place thisorganelle at the center of efforts that will shape the future of regenerativemedicine.展开更多
BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs...BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs were collected from public databases.Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort.Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature(CRS)to score colon cancer patients.A nomogram was developed to evaluate the CRS risk in colon cancer patients.An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy,chemotherapy,and targeted therapy.Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.RESULTS A total of 726 CRGs were collected from public databases.A CRS was constructed,which consisted of the following four genes:TSC1,AXIN2,COPS7A,and MTUS1.Colon cancer patients with a high-risk signature had poor survival.Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+T cells.Regarding treatment response,patients with a high-risk signature were resistant to immunotherapy,chemotherapy,and targeted therapy.COPS7A expression was relatively high in endothelial cells and fibroblasts.MTUS1 expression was high in endothelial cells,fibroblasts,and malignant cells.CONCLUSION We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients,contributing to the development of individualized treatment for colon cancer.展开更多
OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast, and to observe the relationship of its expression with breast cancer pathological features. METHODS The expressio...OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast, and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast （ADH and Peri-PM with ADH）, 50 specimens of breast in situ ductal carcinomas （DCIS）, and 50 specimens of invasive ductal carcinomas （IDC）. Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that： the differences among the 4 groups （normal breast tissues, breast premalignant lesions, DCIS and IDC, P 〈 0.05） were significant, and there were also statistically significant differences between any 2 groups （P 〈 0.05） except for the β-tubulin positive expression comparing DCIS versus IDC （P 〉 0.05）. In addition, β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH （P 〈 0.05）. Following the degree of breast epithelial hyperplasia involved, and its development into carcinoma, the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis （P 〈 0.05）, but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression. Studies of aberrations of centrosomal proteins provide a new way to tumorigenesis. explore the mechanism of breast tumorigenesis.展开更多
Recent development in the field of quantum biology highlights that the intracellular electromagnetic field (EMF) of microtubules plays an important role in many fundamental cellular processes such as mitosis. Here I p...Recent development in the field of quantum biology highlights that the intracellular electromagnetic field (EMF) of microtubules plays an important role in many fundamental cellular processes such as mitosis. Here I propose an intriguing hypothesis that centrosome functions as molecular dynamo to generate electric flow over the microtubules, leading to the electric excitation of microtubule EMF that is required for spindle body microtubule self-assembly. With the help of motors proteins within the centrosome, centrosome transforms the energy from ATP into intracellular EMF in the living cell that shapes the functions of microtubules. There will be a general impact for the cell biology field to understand the mechanistic function of centrosome for the first time in correlation with its structural features. This hypothesis can be tested with technics such as super resolution live cell microscope.展开更多
This paper provides summary description of the procedures by which human and animal cells (eucaryotic cells) divide into two identical parts. The focus is on the nucleus, with particular attention given to the centros...This paper provides summary description of the procedures by which human and animal cells (eucaryotic cells) divide into two identical parts. The focus is on the nucleus, with particular attention given to the centrosome and the chromosome. Within the centrosome is a pair of organelle known as centriole. When the cell is about to divide, the centrioles duplicate themselves. At the same time, the DNA within the chromosome duplicates itself. The centriole pair, now two pairs, then separate with one pair migrating about the nucleus to the diametrically opposite side. The original and migrated centriole then emit long strands known as microtubules across the nucleus. Similarly, the chromosome emits long strands known as kinetochores. The microtubules and the kinetochores are perpendicular to each other and they cover the nucleus with a checkered appearance. The diametrically opposed centriole then forms centrosomes which pull the nucleus apart. The two nuclear parts then separate with each part taking with its half of the remainder of the cell (the cytoplasm) and thus two virtually identical cells are attained. The significance of this paper is that it provides the reader with a condensed summary of the life-dependent process known as cell division.展开更多
This paper provides a mid-level description of cell division and duplication. The focus is on the roles by the chromosomes, centrosomes, microtubules and the kinetochores. The emphasis is on the mechanical activity an...This paper provides a mid-level description of cell division and duplication. The focus is on the roles by the chromosomes, centrosomes, microtubules and the kinetochores. The emphasis is on the mechanical activity and the resulting physical developments. The paper also provides, in its discussion, the harmful effects occurring when duplication procedures go awry. This often leads to unwanted duplication and possibly cancer.展开更多
The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centros...The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centrosome is an important organelle existing in mammalian cells as well as the microtubule organizing center,playing an important role in maintaining vascular structure and homeostasis.This study reviewed the role of centrosome in the regulation of vascular microenvironmental homeostasis.Centrosomal proteins intricately regulate microtubule dynamics and stabilization,and diverse microtubule-relatived cellular activities,including the division,polarization and directional migration of vascular endothelial cells,smooth muscle cells and other types of cells.In addition,primary cilia formed by centrosome are essential in vascular microenvironment.Tumor endothelial cells usually acquire excess centrosomes,and excess centrosomes are regulated by several angiogenic factors.Therefore,uncovering the detailed molecular mechanisms underlying centrosome affecting vascular microenvironmental homeostasis are needed for the treatment of cardiovascular and cerebrovascular diseases.展开更多
NPM1 is a protein-coding gene that encodes the nucleophosmin 1(NPM1)protein.The NPM1 protein exhibits dynamic shuttling between the nucleus and cytoplasm and is involved in various cellular processes,such as centrosom...NPM1 is a protein-coding gene that encodes the nucleophosmin 1(NPM1)protein.The NPM1 protein exhibits dynamic shuttling between the nucleus and cytoplasm and is involved in various cellular processes,such as centrosome duplication,protein chaperoning,and DNA repair.Mutations of the NPM1 gene are associated with human acute myeloid leukemia(AML).AML is a complex hematopoietic cell disorder characterized by excessive proliferation of hematopoietic cells of the myeloid lineage in the bone marrow.This study aimed to predict highly damaging missense single-nucleotide polymorphism(SNPs)in the human NPM1 gene that may be associated with AML.In this investigation,we employed a range of in silico tools to analyze the functional and structural consequences of missense SNPs in the human NPM1 gene.The missense SNPs of the NPM1 gene were retrieved from the Ensembl database.We evaluated the functional and structural impacts of missense SNPs using bioinformatics tools,specifically SIFT,PROVEAN,PolyPhen-2,I-Mutant 3.0,MUpro,and MutPred2.The secondary structure was predicted with PSIPRED.The 3-dimensional structure of the NPM1 protein was obtained from AlphaFold,visualization along with mutant models was generated using PyMOL,and all information about physiological properties was taken from the HOPE project.The protein–protein interactions of the NPM1 protein were investigated using STRING.In silico analysis revealed 8 missense mutations(K54N,I59T,L79S,P152A,K193R,K193N,A283G,and I284F)in the human NPM1 gene.These mutations lead to structural alterations in the protein,which disrupt its normal function and may contribute to the development of AML in humans.展开更多
Background:Dysregulated expression of centrosomal protein 55(CEP55)has been detected in multiple types of cancers.However,the clinical value of CEP55 expression in cancer is controversial.The current meta-analysis qua...Background:Dysregulated expression of centrosomal protein 55(CEP55)has been detected in multiple types of cancers.However,the clinical value of CEP55 expression in cancer is controversial.The current meta-analysis quantitatively investigated the association between CEP55 expression and prognostic outcomes in cancers.Methods:A literature search was performed using the Chinese National Knowledge Infrastructure(CNKI),Wanfang databases,Web of Science,Embase,MEDLINE,PubMed,and Cochrane Library for primary studies.The pooled hazard ratios(HRs)and odds ratios(ORs)were used to investigate the association between CEP55 expression and its prognostic and clinicopatho-logical value in cancers.Results:A total of 12,543 patients from 31 studies were included in this meta-analysis.High CEP55 expression was significantly associated with poor dif-ferentiation,deeper tumor invasion and increased lymph node metastasis in cancer patients.The pooled results indicated that elevated CEP55 expression can predict a poor overall survival(OS)and disease-free survival(DFS)in cancers.These results should be interpreted with caution because of publi-cation bias.However,the pooled HR for OS of lung cancers was 1.50(95%CI=1.36-1.67,p<0.01)with no heterogeneity and publication bias.Conclusions:CEP55 overexpression correlated with poor cancer differentia-tion,deeper tumor invasion,and increased lymph node metastasis,suggesting that CEP55 may serve as a predictive and prognostic biomarker for cancers,especially for lung cancers.展开更多
基金funded by the National Institutes of Health(NIH)Office of Research Infrastructure Programs(P40 OD010440)supported by grants from the National Natural Science Foundation of China(32230016 awarded to S.G.,32270583 awarded to C.Z.,32070619 awarded to X.F.,2023M733425 awarded to X.H.,and 32300438 awarded to X.H.)+2 种基金the National Key R&D Program of China(2022YFA1302700 to S.G.)the Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYPY20230021 awarded to S.G.)the Fundamental Research Funds for the Central Universities。
文摘The centrosome is the microtubule-organizing center and a crucial part of cell division.Centrosomal RNAs(cnRNAs)have been reported to enable precise spatiotemporal control of gene expression during cell division in many species.Whether and how cnRNAs exist in C.elegans are unclear.Here,using the nuclear RNAi Argonaute protein NRDE-3 as a reporter,we observed potential peri-centrosome localized small interfering(si)RNAs in C.elegans.NRDE-3 was previously shown to associate with pre-mRNAs and pre-rRNAs via a process involving the presence of complementary siRNAs.We generated a GFP-NRDE-3 knock-in transgene through CRISPR/Cas9 technology and observed that NRDE-3 formed peri-centrosomal foci neighboring the tubulin protein TBB-2,other centriole proteins and pericentriolar material(PCM)components in C.elegans embryos.The peri-centrosomal accumulation of NRDE-3 depends on RNA-dependent RNA polymerase(RdRP)-synthesized 22G siRNAs and the PAZ domain of NRDE-3,which is essential for siRNA binding.Mutation of eri-1,ergo-1,or drh-3 significantly increased the percentage of pericentrosome-enriched NRDE-3.At the metaphase of the cell cycle,NRDE-3 was enriched in both the peri-centrosomal region and the spindle.Moreover,the integrity of centriole proteins and pericentriolar material(PCM)components is also required for the peri-centrosomal accumulation of NRDE-3.Therefore,we concluded that siRNAs could accumulate in the pericentrosomal region in C.elegans and suggested that the peri-centrosomal region may also be a platform for RNAi-mediated gene regulation.
基金the National Basic Research Program of China(2017YFA0102601,2019YFA0110101,2017YFA0103303)the National Natural Science Foundation of China(31671072,91732301,31771140,81891001)+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences,the Grants of Beijing Brain Initiative of Beijing Municipal Science and Technology Commission(Z181100001518004)Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning.
文摘Cenpj is a centrosomal protein located at the centrosomes and the base of cilia,it plays essential roles in regulating neurogenesis and cerebral cortex development.Although centrosomal and cilium dysfunction are one of the causes of obesity,insulin resistance,and type 2 diabetes,the role that Cenpj plays in the regulation of body weight remains unclear.Here,we deleted Cenpj by crossing Cenpjflox/flox mice with Nkx2.1-Cre mice.Loss of the centrosomal protein Cenpj in Nkx2.1-expressing cells causes morbid obesity in mice at approximately 4 months of age with expended brain ventricles but no change of brain size.We found that hypothalamic cells exhibited reduced proliferation and increased apoptosis upon Cenpj depletion at the embryonic stages,resulting in a dramatic decrease in the number of Proopiomelanocortin(POMC)neurons and electrophysiological dysfunction of NPY neurons in the arcuate nucleus(ARC)in adults.Furthermore,depletion of Cenpj also reduced the neuronal projection from the ARC to the paraventricular nucleus(PVN),with decreased melanocortin-4 receptors(MC4R)expression in PVN neurons.The study defines the roles that Cenpj plays in regulating hypothalamus development and body weight,providing a foundation for further understanding of the pathological mechanisms of related diseases.
基金supported by CAMS Innovation Fund for Medical Sciences(CIFMS)(2024-I2M-C&T-B-089)National Key Research and Development Program(2022YFC2504700,2022YFC2504701,2022YFC2504705)National Natural Science Foundation of China(NSFC81872216).
文摘Introduction:Acral melanoma(AM)is the predominant subtype of cutaneous melanoma in Asian populations,characterized by more aggressive clinical features and limited neoadjuvant therapy response.Centrosomal protein 55 kDa(CEP55)has been implicated in the pathogenesis of various malignancies,but its role in AM remains undefined.Methods:CEP55 expression in melanoma tissues and cell lines was analyzed by RT-qPCR,Western blotting,and immunohistochemistry(IHC).Databases(GEPIA,Sangerbox,Kaplan-Meier plotter,and TIMER)were used to analyze the expression of CEP55 and its correlation with clinical data of melanoma patients.Functional assays were conducted in vitro and in vivo.RNA sequencing(RNA-seq)and rescue experiments were used to explore underlying mechanisms.Tissue microarrays were used to verify the relationship between CEP55 and immune checkpoints.Results:CEP55 overexpression is associated with Breslow thickness and TNM stage in melanoma tissues and cell lines.CEP55 knockdown inhibited melanoma cell proliferation,migration,and invasion.And CEP55 activated mitogen-activated protein kinase(MAPK)signaling,leading to BRAF inhibitor resistance.Besides,CEP55 overexpression was associated with more favorable responses to immunotherapy in melanoma patients.Conclusions:CEP55 plays a critical role in AM progression and immunotherapy.Targeting CEP55 may be a promising therapeutic strategy for AM.
基金supported by the National Nature Science Foundation of China,No.32101020(to JL)the Natural Science Foundation of Shandong Province,Nos.ZR2020MC071(to JL),ZR2023MH327(to HZ)+1 种基金the Integrated Project of Major Research Plan of National Natural Science Foundation of China,No.92249303(to PL)the Natural Science Foundation of Qingdao,No.23-2-1-193-zyyd-jch(to HZ)。
文摘The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.
基金Key Research and Development Foundation supported by Science and Technology Department of Sichuan Province.Project Number:2023YFS0243Project Name:Application of Multiple Nucleic Acid Detection of Respiratory Pathogens Based on Multiple Fusion Curve Technology in Rapid Pathogenic Analysis of Acute Respiratory Distress Syndrome Patients Caused By Atypical Pathogen Infections in Emergency Departments+1 种基金Fund Name:Applied Basic Research Foundation supported by Science and Technology Department of Sichuan Province.Project Number:2021YJ0135Project Name:Explorating the Antiinflammatory Mechanism of Extracellular Vesicles Secreted by Wharton’s Jelly Mesenchymal Stem Cells in Alleviating Pulmonary Vascular Endothelial Injury and Discussing the Effectiveness of VEGF Gene Modification in Sepsis-related ALI/ARDS.
文摘Background:The centrosome,a crucial cellular structure involved in the mitotic process of eukaryotic cells,plays a significant role in tumor progression by regulating the growth and differentiation of neoplastic cells.This makes the centrosome a promising target for therapeutic strategies in cancer treatment.Methods:Utilizing data from the TCGA database,we identified centrosome-related genes and constructed a prognostic model for 518 lung adenocarcinoma patients.Prognosis-associated genes were initially screened using univariate Cox regression,with overfitting minimized by applying LASSO regression to remove collinearity.Finally,a set of 12 genes was selected through multivariable Cox regression for inclusion in the prognostic model.Results:The model’s performance was assessed using ROC curve analysis,demonstrating a robust predictive ability with an AUC of 0.728 in the training group and 0.695 in the validation group.Differential expression analysis between high-risk(HRLAs)and low-risk(LRLAs)individuals was performed,followed by enrichment analyses using KEGG,GO,Progeny,GSVA,and GSEA.These analyses revealed significant differences in immune-related pathways between the two groups.Immune microenvironment assessment through ssGSEA and ESTIMATE indicated that individuals with poor prognosis exhibited lower immune,stromal,and ESTIMATE scores,along with higher tumor purity,suggesting an impaired immune microenvironment in HRLAs patients.Drug susceptibility analysis and molecular docking showed that HRLAs individuals were more responsive to docetaxel,emphasizing the therapeutic relevance of paclitaxel in this cohort.Conclusion:We successfully developed and validated a centrosome-associated gene-based prognostic model,offering clinicians valuable insights for improved decision-making and personalized treatment strategies.This model may facilitate the identification of high-risk patients and guide therapeutic interventions in lung adenocarcinoma.
文摘OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.
基金This work was supported by the National Natural Science Foundation of China (No.30171008) and the Natural Science Foundation of Liaoning Province (No.2001101039).
文摘To explore the relationship between STK15 gene abnormal expression and laryngeal carcinoma. Methods: Tumor tissues and matched normal tissues were taken from 55 LSCC patients. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect STK15 expression in 110 specimens. Results: In 38 of the 55 cases (69.1%), the STK15 expression at the mRNA levels was higher than that of the paired normal tissue. The ratio of ADV (average density value) of STK15 gene to ADV of b-actin gene was 1.220.49 in the cancer tissue, and 0.990.54 in the paired normal tissue with a significant difference (t=4.539, P<0.01). Conclusion: There was obvious association between the STK15 overexpression and laryngeal carcinoma. It may serve as an alternative mechanism of activating the pathogenesis of human laryngeal squamous cell carcinoma.
文摘Colon cancer is currently the third most common cancer and second most fatal cancer in the United States,resulting in approximately 600,000 deaths annually.Though colorectal cancer death rates are decreasing by about 3%every year,disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis,the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments.Colon carcinogenesis is notably a slow process that can take decades.Known factors that contribute to the development of colon cancer are mutational,epigenetic and environmental,and risk factors include age,history of polyps and family history of colon cancer.Colorectal cancers exhibit heterogeneity in their features and are often characterized by the presence of chromosomal instability,microscopic satellite instability,or CpG island methylator phenotype.In this review,we propose that centrosome amplification may be a widespread occurrence in colorectal cancers and could potently influence tumor biology.Moreover,the quantitation of this cancer-specific anomaly could offer valuable prognostic information and pave the way for further customization of treatment based on the organellar profile of patients.Patient stratification models that take into account centrosomal status could thus potentially reduce adverse side effects and result in improved outcomes for colorectal cancer patients.
文摘The objective herein was to connect the ontogeny process of diplochromosomal, amitotic, 4n-skewed division-system, to cytogenetic deficiency lesions in satellite, repetitive DNAs, especially in the chromosomal fragile sites, some 100 distributed over the genome. These latter studies had shown that chemical induced replication-stress led to un-replicated lesions in these fragile sites, which from inaccurate repair processes caused genomic instability. In the chain of events of the ontogeny process to the special tetraploidy, it was proposed that primary damaged human cells could undergo replication stress from repair-process present during cell replication, a suggestion verified by X-ray damaged cells producing the unstable fragile sites (see text). The cancer-importance for therapy is recognition of cell cycle change for the 4n derivative fitness-gained, diploid progeny cells. An open question is whether RB controlling G1 to S-period is mutated at this suggested tumorigenesis initiating phase, and if so, with what consequences for therapy. The fragile site studies further showed that repair of repetitive DNAs could produce two types of genomic changes: single gene mutations and CNVs, which were here shown to be chromosomally located on “borders” to repairing satellite lesions. This genomic placement was found to correspond to mutations identified in tumor sequencing (p53, Rb, MYC), favoring a bad luck location for their cancer “mutational nature”. The CNVs in cancers, are here seen as molecular expressions of long-known cytogenetic HSRs and DMs also with demonstrated origin from amplifications of single genes. Over-expression of oncogenes was hinted of being from duplications, but Drosophila genetics demonstrated the opposite, gene inactivation. The reduced eye-size from dominant, BAR-Ultra-Bar-eye phenotypes, was caused by duplications, inactivating the genetic system for eye-size. The finding of CNVs showing “evasion” of the immune system suggests, inactivation of immune-determining genetics. Since mutated genes on borders to satellite DNAs are a fact in hematological cancers, the 4n-skewed division-system is suggested to replace debated leukemogenesis with fitness-gain from molecular mutations. For these cancers the question is how normal bone marrow cells attain genomic damage for special tetraploidy, which was referred to studies of cells moving in artificial marrow-like substrate, needing serious attention.
文摘Sperm are a highly specialized cell type derived to deliver the paternal haploid genome to the oocyte. The epigenetic, or gene regulatory, properties and mechanisms of the sperm assist in preparation of the paternal genome to contribute to embryogenesis and the genome of the zygote. Many recent studies have addressed the issue of altered epigenetic processes in the sperm. This review evaluates the current understanding of DNA damage, chromosome aneuploidy, reduced telomere length, malformations of the centrosome, genomic imprinting errors, altered mRNA profiles, and abnormal nuclear packaging in the sperm prior to fertilization and the observed effects on embryogenesis. Attention has also been given to understanding the underlying etiology of sperm with altered epigenetic mechanisms in humans. （Asian J Androl 2006 Mar; 8： 131-142）
基金Natural Science Foundation of Zhejiang Province,China(No.LY20H040010).
文摘Mitotic kinesin KIFC1 plays critical roles in mitosis by regulating the spindle length,pole formation,and known for clustering extra centrosomes in cancer cells.Centrosome clustering is associated with the survival of cancer cells,but this phenomenon remains obscure in prostate cancer(PCa).The present study demonstrated that PCa cells showed centrosome amplification and clustering during interphase and mitosis,respectively.KIFC1 is highly expressed in PCa cells and tumor tissues of prostatic adenocarcinoma(PAC)patients.Up-regulation of KIFC1 facilitated the PCa cell survival in vitro by ensuring bipolar mitosis through clustering the multiple centrosomes,suggesting centrosome clustering could be a leading cause of prostate carcinogenesis.Conversely,the silencing of KIFC1 resulted in normal centrosome number or multipolar mitosis by inhibiting the clustering of amplified centrosomes in PCa cells.Besides,knockdown of KIFC1 by RNAi in PCa cells reduced cancer cell survival,and proliferation.KIFC1 interacted with centrosome structural protein Centrin 2 in clustering of amplified centrosomes in PCa cells to ensure the bipolar mitotic spindle formation.Knockdown of Centrin 2 in PCa cells inhibited the centrosome amplification and clustering.Moreover,up-regulated KIFC1 promotes PCa cell proliferation via progression of cell cycle possibly through aberrant activation of cyclin dependent kinase 1(Cdk1).Therefore,KIFC1 can be a prognostic marker and therapeutic target of PCa for inhibiting the cancer cell proliferation.
文摘At the core of regenerative medicine lies the expectation of repair or replacementof damaged tissues or whole organs. Donor scarcity and transplant rejection aremajor obstacles, and exactly the obstacles that stem cellbased therapy promisesto overcome. These therapies demand a comprehensive understanding of theasymmetric division of stem cells, i.e. their ability to produce cells with identicalpotency or differentiated cells. It is believed that with better understanding,researchers will be able to direct stem cell differentiation. Here, we describeextraordinary advances in manipulating stem cell fate that show that we need tofocus on the centrosome and the centrosome-derived primary cilium. This beliefcomes from the fact that this organelle is the vehicle that coordinates theasymmetric division of stem cells. This is supported by studies that report thesignificant role of the centrosome/cilium in orchestrating signaling pathways thatdictate stem cell fate. We anticipate that there is sufficient evidence to place thisorganelle at the center of efforts that will shape the future of regenerativemedicine.
基金Supported by Heilongjiang Postdoctoral Fund,No.LBH-Z18214Haiyan Foundation of Harbin Medical University Cancer Hospital,No.JJQN2014-06Foundation of Health Commission of Heilongjiang Province,No.2016-096.
文摘BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs were collected from public databases.Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort.Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature(CRS)to score colon cancer patients.A nomogram was developed to evaluate the CRS risk in colon cancer patients.An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy,chemotherapy,and targeted therapy.Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.RESULTS A total of 726 CRGs were collected from public databases.A CRS was constructed,which consisted of the following four genes:TSC1,AXIN2,COPS7A,and MTUS1.Colon cancer patients with a high-risk signature had poor survival.Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+T cells.Regarding treatment response,patients with a high-risk signature were resistant to immunotherapy,chemotherapy,and targeted therapy.COPS7A expression was relatively high in endothelial cells and fibroblasts.MTUS1 expression was high in endothelial cells,fibroblasts,and malignant cells.CONCLUSION We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients,contributing to the development of individualized treatment for colon cancer.
基金This work was supported by a grant from the National Natural Science Foundation of China(No.30471967)
文摘OBJECTIVE To explore the expression of β-tubulin in premalignant lesions and carcinomas of the breast, and to observe the relationship of its expression with breast cancer pathological features. METHODS The expression of β-tubulin was detected immunohistochemically in 50 specimens of premalignant lesions of the breast （ADH and Peri-PM with ADH）, 50 specimens of breast in situ ductal carcinomas （DCIS）, and 50 specimens of invasive ductal carcinomas （IDC）. Thirty specimens of normal breast tissues served as a control group. RESULTS Immunohistochemical analysis showed that： the differences among the 4 groups （normal breast tissues, breast premalignant lesions, DCIS and IDC, P 〈 0.05） were significant, and there were also statistically significant differences between any 2 groups （P 〈 0.05） except for the β-tubulin positive expression comparing DCIS versus IDC （P 〉 0.05）. In addition, β-tubulin was expressed at a higher level in Peri-PM with ADH compared to ADH （P 〈 0.05）. Following the degree of breast epithelial hyperplasia involved, and its development into carcinoma, the β-tubulin positive expression displayed an elevating tendency. We also found a significant positive relationship of β-tubulin expression with lymph node metastasis （P 〈 0.05）, but no significant correlation with histological grading and nuclear grade. CONCLUSION Centrosome defects may be an early event in the development of breast cancer and they can also promote tumor progression. Studies of aberrations of centrosomal proteins provide a new way to tumorigenesis. explore the mechanism of breast tumorigenesis.
文摘Recent development in the field of quantum biology highlights that the intracellular electromagnetic field (EMF) of microtubules plays an important role in many fundamental cellular processes such as mitosis. Here I propose an intriguing hypothesis that centrosome functions as molecular dynamo to generate electric flow over the microtubules, leading to the electric excitation of microtubule EMF that is required for spindle body microtubule self-assembly. With the help of motors proteins within the centrosome, centrosome transforms the energy from ATP into intracellular EMF in the living cell that shapes the functions of microtubules. There will be a general impact for the cell biology field to understand the mechanistic function of centrosome for the first time in correlation with its structural features. This hypothesis can be tested with technics such as super resolution live cell microscope.
文摘This paper provides summary description of the procedures by which human and animal cells (eucaryotic cells) divide into two identical parts. The focus is on the nucleus, with particular attention given to the centrosome and the chromosome. Within the centrosome is a pair of organelle known as centriole. When the cell is about to divide, the centrioles duplicate themselves. At the same time, the DNA within the chromosome duplicates itself. The centriole pair, now two pairs, then separate with one pair migrating about the nucleus to the diametrically opposite side. The original and migrated centriole then emit long strands known as microtubules across the nucleus. Similarly, the chromosome emits long strands known as kinetochores. The microtubules and the kinetochores are perpendicular to each other and they cover the nucleus with a checkered appearance. The diametrically opposed centriole then forms centrosomes which pull the nucleus apart. The two nuclear parts then separate with each part taking with its half of the remainder of the cell (the cytoplasm) and thus two virtually identical cells are attained. The significance of this paper is that it provides the reader with a condensed summary of the life-dependent process known as cell division.
文摘This paper provides a mid-level description of cell division and duplication. The focus is on the roles by the chromosomes, centrosomes, microtubules and the kinetochores. The emphasis is on the mechanical activity and the resulting physical developments. The paper also provides, in its discussion, the harmful effects occurring when duplication procedures go awry. This often leads to unwanted duplication and possibly cancer.
文摘The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centrosome is an important organelle existing in mammalian cells as well as the microtubule organizing center,playing an important role in maintaining vascular structure and homeostasis.This study reviewed the role of centrosome in the regulation of vascular microenvironmental homeostasis.Centrosomal proteins intricately regulate microtubule dynamics and stabilization,and diverse microtubule-relatived cellular activities,including the division,polarization and directional migration of vascular endothelial cells,smooth muscle cells and other types of cells.In addition,primary cilia formed by centrosome are essential in vascular microenvironment.Tumor endothelial cells usually acquire excess centrosomes,and excess centrosomes are regulated by several angiogenic factors.Therefore,uncovering the detailed molecular mechanisms underlying centrosome affecting vascular microenvironmental homeostasis are needed for the treatment of cardiovascular and cerebrovascular diseases.
文摘NPM1 is a protein-coding gene that encodes the nucleophosmin 1(NPM1)protein.The NPM1 protein exhibits dynamic shuttling between the nucleus and cytoplasm and is involved in various cellular processes,such as centrosome duplication,protein chaperoning,and DNA repair.Mutations of the NPM1 gene are associated with human acute myeloid leukemia(AML).AML is a complex hematopoietic cell disorder characterized by excessive proliferation of hematopoietic cells of the myeloid lineage in the bone marrow.This study aimed to predict highly damaging missense single-nucleotide polymorphism(SNPs)in the human NPM1 gene that may be associated with AML.In this investigation,we employed a range of in silico tools to analyze the functional and structural consequences of missense SNPs in the human NPM1 gene.The missense SNPs of the NPM1 gene were retrieved from the Ensembl database.We evaluated the functional and structural impacts of missense SNPs using bioinformatics tools,specifically SIFT,PROVEAN,PolyPhen-2,I-Mutant 3.0,MUpro,and MutPred2.The secondary structure was predicted with PSIPRED.The 3-dimensional structure of the NPM1 protein was obtained from AlphaFold,visualization along with mutant models was generated using PyMOL,and all information about physiological properties was taken from the HOPE project.The protein–protein interactions of the NPM1 protein were investigated using STRING.In silico analysis revealed 8 missense mutations(K54N,I59T,L79S,P152A,K193R,K193N,A283G,and I284F)in the human NPM1 gene.These mutations lead to structural alterations in the protein,which disrupt its normal function and may contribute to the development of AML in humans.
基金The 2022 Shenzhen Third People's Hospital Second Batch Medicine Research Project,Grant/Award Number:G2022129。
文摘Background:Dysregulated expression of centrosomal protein 55(CEP55)has been detected in multiple types of cancers.However,the clinical value of CEP55 expression in cancer is controversial.The current meta-analysis quantitatively investigated the association between CEP55 expression and prognostic outcomes in cancers.Methods:A literature search was performed using the Chinese National Knowledge Infrastructure(CNKI),Wanfang databases,Web of Science,Embase,MEDLINE,PubMed,and Cochrane Library for primary studies.The pooled hazard ratios(HRs)and odds ratios(ORs)were used to investigate the association between CEP55 expression and its prognostic and clinicopatho-logical value in cancers.Results:A total of 12,543 patients from 31 studies were included in this meta-analysis.High CEP55 expression was significantly associated with poor dif-ferentiation,deeper tumor invasion and increased lymph node metastasis in cancer patients.The pooled results indicated that elevated CEP55 expression can predict a poor overall survival(OS)and disease-free survival(DFS)in cancers.These results should be interpreted with caution because of publi-cation bias.However,the pooled HR for OS of lung cancers was 1.50(95%CI=1.36-1.67,p<0.01)with no heterogeneity and publication bias.Conclusions:CEP55 overexpression correlated with poor cancer differentia-tion,deeper tumor invasion,and increased lymph node metastasis,suggesting that CEP55 may serve as a predictive and prognostic biomarker for cancers,especially for lung cancers.
