Jie Chen, Shan Wu, Jie‐Jie He, Yu‐Peng Liu, Zhao‐Yang Deng, Han‐Kai Fang, Jian‐Fan Chen, Ya‐Lan Wei, Zhen‐Yu She
{"title":"Kinesin‐7 CENP‐E mediates centrosome organization and spindle assembly to regulate chromosome alignment and genome stability","authors":"Jie Chen, Shan Wu, Jie‐Jie He, Yu‐Peng Liu, Zhao‐Yang Deng, Han‐Kai Fang, Jian‐Fan Chen, Ya‐Lan Wei, Zhen‐Yu She","doi":"10.1111/cpr.13745","DOIUrl":"https://doi.org/10.1111/cpr.13745","url":null,"abstract":"Chromosome congression and alignment are essential for cell cycle progression and genomic stability. Kinesin‐7 CENP‐E, a plus‐end‐directed kinesin motor, is required for chromosome biorientation, congression and alignment in cell division. However, it remains unclear how chromosomes are aligned and segregated in the absence of CENP‐E in mitosis. In this study, we utilize the CRISPR‐Cas9 gene editing method and high‐throughput screening to establish <jats:italic>CENP‐E</jats:italic> knockout cell lines and reveal that <jats:italic>CENP‐E</jats:italic> deletion results in defects in chromosome congression, alignment and segregation, which further promotes aneuploidy and genomic instability in mitosis. Both CENP‐E inhibition and deletion lead to the dispersion of spindle poles, the formation of the multipolar spindle and spindle disorganization, which indicates that CENP‐E is necessary for the organization and maintenance of spindle poles. In addition, <jats:italic>CENP‐E</jats:italic> heterozygous deletion in spleen tissues also leads to the accumulation of dividing lymphocytes and cell cycle arrest in vivo. Furthermore, <jats:italic>CENP‐E</jats:italic> deletion also disrupts the localization of key kinetochore proteins and triggers the activation of the spindle assembly checkpoint. In summary, our findings demonstrate that CENP‐E promotes kinetochore‐microtubule attachment and spindle pole organization to regulate chromosome alignment and spindle assembly checkpoint during cell division.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"9 1","pages":""},"PeriodicalIF":8.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danling Liu, Yunzhong Zhang, Luo Guo, Rui Fang, Jin Guo, Peifang Li, Tingting Qian, Wen Li, Liping Zhao, Xiaoning Luo, Siyi Zhang, Jun Shao, Shan Sun
{"title":"Single-cell atlas of healthy vocal folds and cellular function in the endothelial-to-mesenchymal transition.","authors":"Danling Liu, Yunzhong Zhang, Luo Guo, Rui Fang, Jin Guo, Peifang Li, Tingting Qian, Wen Li, Liping Zhao, Xiaoning Luo, Siyi Zhang, Jun Shao, Shan Sun","doi":"10.1111/cpr.13723","DOIUrl":"https://doi.org/10.1111/cpr.13723","url":null,"abstract":"<p><p>The vocal fold is an architecturally complex organ comprising a heterogeneous mixture of various layers of individual epithelial and mesenchymal cell lineages. Here we performed single-cell RNA sequencing profiling of 5836 cells from the vocal folds of adult Sprague-Dawley rats. Combined with immunostaining, we generated a spatial and transcriptional map of the vocal fold cells and characterized the subpopulations of epithelial cells, mesenchymal cells, endothelial cells, and immune cells. We also identified a novel epithelial-to-mesenchymal transition-associated epithelial cell subset that was mainly found in the basal epithelial layers. We further confirmed that this subset acts as intermediate cells with similar genetic features to epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma. Finally, we present the complex intracellular communication network involved homeostasis using CellChat analysis. These studies define the cellular and molecular framework of the biology and pathology of the VF mucosa and reveal the functional importance of developmental pathways in pathological states in cancer.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13723"},"PeriodicalIF":5.9,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuai Zhu, Jiashuo Li, Xiuwan Wang, Yifei Jin, Hengjie Wang, Huiqing An, Hongzheng Sun, Longsen Han, Bin Shen, Qiang Wang
{"title":"The chromatin accessibility landscape of mouse oocytes during configuration transition.","authors":"Shuai Zhu, Jiashuo Li, Xiuwan Wang, Yifei Jin, Hengjie Wang, Huiqing An, Hongzheng Sun, Longsen Han, Bin Shen, Qiang Wang","doi":"10.1111/cpr.13733","DOIUrl":"https://doi.org/10.1111/cpr.13733","url":null,"abstract":"<p><p>The transition of chromatin configuration in mammalian oocytes from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) is critical for acquiring the developmental competence. However, the genomic and epigenomic features underlying this process remain poorly understood. In the present study, we first establish the chromatin accessibility landscape of mouse oocytes from NSN to SN stage. Through the integrative analysis of multi-omics, we find that the establishment of DNA methylation in oocytes is independent of the dynamics of chromatin accessibility. In contrast, histone H3K4me3 status is closely associated with the dynamics of accessible regions during configuration transition. Furthermore, by focusing on the actively transcribed genes in NSN and SN oocytes, we discover that chromatin accessibility coupled with histone methylation (H3K4me3 and H3K27me3) participates in the transcriptional control during phase transition. In sum, our data provide a comprehensive resource for probing configuration transition in oocytes, and offer insights into the mechanisms determining chromatin dynamics and oocyte quality.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13733"},"PeriodicalIF":5.9,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Featured Cover","authors":"Yuhao Liu, Kechen Li, Weijie Zhuang, Lulu Liang, Xiangyi Chen, Dongsheng Yu","doi":"10.1111/cpr.13744","DOIUrl":"https://doi.org/10.1111/cpr.13744","url":null,"abstract":"<p>The cover image is based on the article <i>Tetrahedral framework nucleic acid–based small-molecule inhibitor delivery for ecological prevention of biofilm</i> by Yuhao Liu et al., https://doi.org/10.1111/cpr.13678. \u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"57 9","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.13744","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell transcriptomic analysis of the senescent microenvironment in bone metastasis.","authors":"Shenglin Wang, Lu Ao, Huangfeng Lin, Hongxiang Wei, Zhaoyang Wu, Shuting Lu, Fude Liang, Rongkai Shen, Huarong Zhang, Tongjie Miao, Xiaopei Shen, Jianhua Lin, Guangxian Zhong","doi":"10.1111/cpr.13743","DOIUrl":"https://doi.org/10.1111/cpr.13743","url":null,"abstract":"<p><p>Bone metastasis (BM) is a mortality-related event of late-stage cancer, with non-small cell lung cancer (NSCLC) being a common origin for BM. However, the detailed molecular profiling of the metastatic bone ecosystem is not fully understood, hindering the development of effective therapies for advanced patients. In this study, we examined the cellular heterogeneity between primary tumours and BM from tissues and peripheral blood by single-cell transcriptomic analysis, which was verified using multiplex immunofluorescence staining and public datasets. Our results demonstrate a senescent microenvironment in BM tissues of NSCLC. BM has a significantly higher infiltration of malignant cells with senescent characteristics relative to primary tumours, accompanied by aggravated metastatic properties. The endothelial-mesenchymal transition involved with SOX18 activation is related to the cellular senescence of vascular endothelial cells from BM. CD4Tstr cells, with pronounced stress and senescence states, are preferentially infiltrated in BM, indicating stress-related dysfunction contributing to the immunocompromised environment during tumour metastasis to bone. Moreover, we identify the SPP1 pathway-induced cellular crosstalk among T cells, vascular ECs and malignant cells in BM, which activates SOX18 and deteriorates patient survival. Our findings highlight the roles of cellular senescence in modulating the microenvironment of BM and implicate anti-senescence therapy for advanced NSCLC patients.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13743"},"PeriodicalIF":5.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Teresa Rossi, Egidio Iorio, Mattea Chirico, Maria Elena Pisanu, Nicola Amodio, Maria Eugenia Gallo Cantafio, Ida Perrotta, Francesca Colciaghi, Marco Fiorillo, Alessia Gianferrari, Noemi Puccio, Antonino Neri, Alessia Ciarrocchi, Mariaelena Pistoni
{"title":"BET inhibitors (BETi) influence oxidative phosphorylation metabolism by affecting mitochondrial dynamics leading to alterations in apoptotic pathways in triple-negative breast cancer (TNBC) cells.","authors":"Teresa Rossi, Egidio Iorio, Mattea Chirico, Maria Elena Pisanu, Nicola Amodio, Maria Eugenia Gallo Cantafio, Ida Perrotta, Francesca Colciaghi, Marco Fiorillo, Alessia Gianferrari, Noemi Puccio, Antonino Neri, Alessia Ciarrocchi, Mariaelena Pistoni","doi":"10.1111/cpr.13730","DOIUrl":"https://doi.org/10.1111/cpr.13730","url":null,"abstract":"<p><p>Repressing BET proteins' function using bromodomain inhibitors (BETi) has been shown to elicit antitumor effects by regulating the transcription of genes downstream of BRD4. We previously showed that BETi promoted cell death of triple-negative breast cancer (TNBC) cells. Here, we proved that BETi induce altered mitochondrial dynamics fitness in TNBC cells falling in cell death. We demonstrated that BETi treatment downregulated the expression of BCL-2, and proteins involved in mitochondrial fission and increased fused mitochondria. Impaired mitochondrial fission affected oxidative phosphorylation (OXPHOS) inducing the expression of OXPHOS-related genes, SDHa and ATP5a, and increased cell death. Consistently, the amount of mitochondrial DNA and mitochondrial membrane potential (∆Ψm) increased in BETi-treated cells compared to control cells. Lastly, BETi in combination with Metformin reduced cell growth. Our results indicate that mitochondrial dynamics and OXPHOS metabolism support breast cancer proliferation and represent novel BETi downstream targets in TNBC cells.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13730"},"PeriodicalIF":5.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuai Mei, Xiaozhu Ma, Li Zhou, Qidamugai Wuyun, Ziyang Cai, Jiangtao Yan, Hu Ding
{"title":"CircSMAD3 represses VSMC phenotype switching and neointima formation via promoting hnRNPA1 ubiquitination degradation.","authors":"Shuai Mei, Xiaozhu Ma, Li Zhou, Qidamugai Wuyun, Ziyang Cai, Jiangtao Yan, Hu Ding","doi":"10.1111/cpr.13742","DOIUrl":"https://doi.org/10.1111/cpr.13742","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are novel regulatory RNAs with high evolutionary conservation and stability, which makes them effective therapeutic agents for various vascular diseases. The SMAD family is a downstream mediator of the canonical transforming growth factor beta (TGF-β) signalling pathway and has been considered as a critical regulator in vascular injury. However, the role of circRNAs derived from the SMAD family members in vascular physiology remains unclear. In this study, we initially identified potential functional circRNAs originating from the SMAD family using integrated transcriptome screening. circSMAD3, derived from the SMAD3 gene, was identified to be significantly downregulated in vascular injury and atherosclerosis. Transcriptome analysis was conducted to comprehensively illustrate the pathways modulated by circRNAs. Functionally, circSMAD3 repressed vascular smooth muscle cell (VSMC) proliferation and phenotype switching in vitro evidenced by morphological assays, and ameliorated arterial injury-induced neointima formation in vivo. Mechanistically, circSMAD3 interacted with heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) within the nucleus, enhanced its interaction with E3 ligase WD repeat domain 76 to promote hnRNPA1 ubiquitination degradation, facilitated p53 pre-RNA splicing, activated the p53γ signalling pathway, and finally suppressed VSMC proliferation and phenotype switching. Our study identifies circSMAD3 as a novel epigenetic regulator that suppresses VSMC proliferation and phenotype switching, thereby attenuating vascular remodelling and providing a new circRNA-based therapeutic strategy for cardiovascular diseases.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13742"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meng-Jie Zhang, Wen-Ping Lin, Qing Wang, Shuo Wang, An Song, Yuan-Yuan Wang, Hao Li, Zhi-Jun Sun
{"title":"Oncolytic herpes simplex virus propagates tertiary lymphoid structure formation via CXCL10/CXCR3 to boost antitumor immunity.","authors":"Meng-Jie Zhang, Wen-Ping Lin, Qing Wang, Shuo Wang, An Song, Yuan-Yuan Wang, Hao Li, Zhi-Jun Sun","doi":"10.1111/cpr.13740","DOIUrl":"https://doi.org/10.1111/cpr.13740","url":null,"abstract":"<p><p>Inducing tertiary lymphoid structure (TLS) formation can fuel antitumor immunity. It is necessary to create mouse models containing TLS to explore strategies of TLS formation. Oncolytic herpes simplex virus-1 (oHSV) exhibited intense effects in preclinical and clinical trials. However, the role of oHSV in TLS formation remains to be elucidated. Here, we observed the presence of TLS in 4MOSC1 and MC38 subcutaneous tumour models. Interestingly, oHSV evoked TLS formation, and increased infiltration of B cells and stem-like TCF1<sup>+</sup>CD8<sup>+</sup> T cells proliferation. Mechanistically, oHSV increased the expression of TLS-related chemokines, along with upregulated CXCL10/CXCR3 to facilitate TLS formation. Notably, CXCL10 and CXCR3 were favourable prognostic factors for cancer patients, and closely related with immune cells infiltration. Inhibiting CXCL10/CXCR3 reduced TCF1<sup>+</sup>CD8<sup>+</sup> T cells and granzyme B expression, and impaired oHSV-mediated TLS formation. Furthermore, oHSV-mediated TLS formation revealed superior response and survival rate when combined with αPD-1 treatment. Collectively, these findings indicate that oHSV recruits stem-like TCF1<sup>+</sup>CD8<sup>+</sup> T cells through CXCL10/CXCR3 pathway to propagate TLS formation, and warrants future antitumor immunity development.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13740"},"PeriodicalIF":5.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tina Meißgeier, Melanie Kappelmann-Fenzl, Sebastian Staebler, Ata Jadid Ahari, Christian Mertes, Julien Gagneur, Lisa Linck-Paulus, Anja Katrin Bosserhoff
{"title":"Splicing control by PHF5A is crucial for melanoma cell survival.","authors":"Tina Meißgeier, Melanie Kappelmann-Fenzl, Sebastian Staebler, Ata Jadid Ahari, Christian Mertes, Julien Gagneur, Lisa Linck-Paulus, Anja Katrin Bosserhoff","doi":"10.1111/cpr.13741","DOIUrl":"https://doi.org/10.1111/cpr.13741","url":null,"abstract":"<p><p>Abnormalities in alternative splicing are a hallmark of cancer formation. In this study, we investigated the role of the splicing factor PHD finger protein 5A (PHF5A) in melanoma. Malignant melanoma is the deadliest form of skin cancer, and patients with a high PHF5A expression show poor overall survival. Our data revealed that an siRNA-mediated downregulation of PHF5A in different melanoma cell lines leads to massive splicing defects of different tumour-relevant genes. The loss of PHF5A results in an increased rate of apoptosis by triggering Fas- and unfolded protein response (UPR)-mediated apoptosis pathways in melanoma cells. These findings are tumour-specific because we did not observe this regulation in fibroblasts. Our study identifies a crucial role of PHF5A as driver for melanoma malignancy and the described underlying splicing network provides an interesting basis for the development of new therapeutic targets for this aggressive form of skin cancer.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13741"},"PeriodicalIF":5.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiyuan Wu, Wei Li, Melissa Tan, Faith Yuan Xin How, Haripriya Sadhasivan, Ratha Mahendran, Qinghui Wu, Edmund Chiong, Minh T N Le
{"title":"IL-12 minicircle delivery via extracellular vesicles as immunotherapy for bladder cancer.","authors":"Zhiyuan Wu, Wei Li, Melissa Tan, Faith Yuan Xin How, Haripriya Sadhasivan, Ratha Mahendran, Qinghui Wu, Edmund Chiong, Minh T N Le","doi":"10.1111/cpr.13739","DOIUrl":"https://doi.org/10.1111/cpr.13739","url":null,"abstract":"<p><p>Interleukin-12 (IL-12) holds significant potential in cancer therapy; however, its clinical applicability is hindered by dose-limiting toxicity. Delivery of the IL-12 gene directly to tumours for constitutive IL-12 expression is a possible strategy to enhance its effectiveness while minimizing systemic toxicity. In this study, we investigate the potential of red blood cell-derived extracellular vesicles (RBCEVs) as a carrier for Il-12 plasmid delivery. We demonstrate that RBCEVs can be loaded with minicircle plasmid encoding IL-12 and delivered to MB49 bladder cancer cells for IL-12 expression. The expression of transgenes from minicircles was significantly higher than from the parental plasmids. RBCEV-mediated IL-12 expression stimulated immune responses in mouse splenocytes. Intratumoral delivery of Il-12 plasmid-loaded RBCEVs suppressed bladder cancer tumour growth, stimulated immune responses and promoted immune cell infiltration. In conclusion, our study demonstrates the promising potential of RBCEVs as an effective, safe and redosable nucleic acid drug delivery platform for IL-12.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13739"},"PeriodicalIF":5.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}