Cell Cycle最新文献

{"title":"c-Jun and Fra-2 pair up to Myc-anistically drive HCC.","authors":"Latifa Bakiri, Erwin F Wagner","doi":"10.1080/15384101.2024.2429968","DOIUrl":"https://doi.org/10.1080/15384101.2024.2429968","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), a leading cause of cancer-related death with limited therapies, is a complex disease developing in a background of Hepatitis Virus infection or systemic conditions, such as the metabolic syndrome. Investigating HCC pathogenesis in model organisms is therefore crucial for developing novel diagnostic and therapeutic tools. Genetically engineered mouse models (GEMMs) have been instrumental in recapitulating the local and systemic features of HCC. Early studies using GEMMs and patient material implicated members of the dimeric Activator Protein-1 (AP-1) transcription factor family, such as c-Jun and c-Fos, in HCC formation. In a recent report, we described how switchable, hepatocyte-restricted expression of a single-chain c-Jun~Fra-2 protein, functionally mimicking the c-Jun/Fra-2 AP-1 dimer, results in spontaneous and largely reversible liver tumors in GEMMs. Dysregulated cell cycle, inflammation, and dyslipidemia are observed at early stages and tumors display molecular HCC signatures. We demonstrate that increased c-Myc expression is an essential molecular determinant of tumor formation that can be therapeutically targeted using the BET inhibitor JQ1. Here, we discuss these findings with additional results illustrating how AP-1 GEMMs can foster preclinical research on liver diseases with novel perspectives offered by the constantly increasing wealth of HCC-related datasets.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-9"},"PeriodicalIF":3.4,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: DDB2 association with PCNA is required for its degradation after UV-induced DNA damage.","authors":"","doi":"10.1080/15384101.2024.2396717","DOIUrl":"https://doi.org/10.1080/15384101.2024.2396717","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy unrelated transcriptional mechanisms of hydroxychloroquine resistance revealed by integrated multi-omics of evolved cancer cells.","authors":"Silvia G Vaena, Martin J Romeo, Mirna Mina-Abouda, Emma C Funk, George Fullbright, David T Long, Joe R Delaney","doi":"10.1080/15384101.2024.2402191","DOIUrl":"10.1080/15384101.2024.2402191","url":null,"abstract":"<p><p>Hydroxychloroquine (HCQ) and chloroquine are repurposed drugs known to disrupt autophagy, a molecular recycling pathway essential for tumor cell survival, chemotherapeutic resistance, and stemness. We pursued a multi-omic strategy in OVCAR3 ovarian cancer and CCL218 colorectal cancer cells. Two genome-scale screens were performed. In the forward genetic screen, cell populations were passaged for 15 drug pulse-chases with HCQ or vehicle control. Evolved cells were collected and processed for bulk RNA-seq, exome-seq, and single-cell RNA-seq (scRNA-seq). In the reverse genetic screen, a pooled CRISPR-Cas9 library was used in cells over three pulse-chases of HCQ or vehicle control treatments. HCQ evolved cells displayed remarkably few mutational differences, but substantial transcriptional differences. Transcriptomes revealed multiple pathways associated with resistance to HCQ, including upregulation of glycolysis, exocytosis, and chromosome condensation/segregation, or downregulation of translation and apoptosis. The Cas9 screen identified only one autophagy gene. Chromosome condensation and segregation were confirmed to be disrupted by HCQ in live cells and organelle-free <i>in vitro</i> extracts. Transcriptional plasticity was the primary mechanism by which cells evolved resistance to HCQ. Neither autophagy nor the lysosome were substantive hits. Our analysis may serve as a model for how to better position repurposed drugs in oncology.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-21"},"PeriodicalIF":3.4,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin protects against defects induced by methoxychlor in porcine oocyte maturation.","authors":"Zhaojun Geng, Mingjun Zhang, Shuming Shi, Bing Hu, Liying Liu, Zhichao Chi, Linyi Qu, Yongxun Jin, Xianfeng Yu","doi":"10.1080/15384101.2024.2402190","DOIUrl":"https://doi.org/10.1080/15384101.2024.2402190","url":null,"abstract":"<p><p>Methoxychlor (MXC) is a widely used organochlorine pesticide primarily targeting pests. However, MXC has been found to negatively impact the reproductive system of both humans and animals, triggering oxidative stress and apoptosis. Melatonin (MLT), an endogenous hormone, possesses various benefits, including circadian rhythm regulation and anti-inflammatory and antioxidative stress effects. Moreover, MLT plays a crucial role in the development of animal germ cells and embryos. This study aimed to investigate the impact of MLT on porcine oocytes exposed to MXC. The experimental findings revealed that 200 μM MXC had detrimental effects on the maturation of porcine oocytes. However, the addition of 10^-8 M MLT mitigated the toxic effects of MXC. MXC induced oxidative stress in porcine oocytes, leading to an increase in reactive oxygen species and impairing mitochondrial function. Consequently, oocyte quality was affected, resulting in elevated levels of early apoptosis and DNA damage, ultimately negatively impacting subsequent embryonic development. However, the addition of MLT showed the potential to ameliorate the damage caused by MXC. In conclusion, our results suggest that MLT exhibits a protective effect against MXC-induced damage to porcine oocyte maturation.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-17"},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell cycle regulated expression of the <i>WHI7</i> Start repressor gene.","authors":"Cristina Ros-Carrero, Mercè Gomar-Alba, J Carlos Igual","doi":"10.1080/15384101.2024.2402192","DOIUrl":"https://doi.org/10.1080/15384101.2024.2402192","url":null,"abstract":"<p><p>Periodic transcriptional waves along the cell cycle ensure the accurate progression of the different cell cycle phases through the timely regulated expression of cell cycle proteins. The G1/S transition (Start) consists in the activation of a transcriptional program by G1 CDKs through the inactivation of Start transcriptional repressors, Whi5 and Whi7 in yeast or Rb in mammals. Here, we provide a comprehensive characterization of the transcriptional regulation of the Start repressor Whi7 in budding yeast. We found that <i>WHI7</i> is a cell cycle regulated gene that shows periodic expression peaking in G1. Our results demonstrate that the three cell cycle transcriptional programs related to G1 and their corresponding transcription factors are involved in the transcriptional control of <i>WHI7</i>. Specifically, we identified that the transcriptional regulators Swi5 and Mcm1-Yox1, which are involved in late M and early G1 expression, and the transcription factors MBF and SBF, which are responsible for G1/S expression, are able to associate and regulate the <i>WHI7</i> gene. In summary, in this work, we provide new mechanisms for the regulation of the Start repressor Whi7, which highlights the precise and complex control of the cell cycle machinery governing the G1/S transition.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-17"},"PeriodicalIF":3.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing precision in colorectal cancer surgery: development of an LGR5-targeting RSPO1 peptide mimetic as a contrast agent for intraoperative fluorescence molecular imaging.","authors":"Erika Parasido, Patricia Ribeiro, Ramesh M Chingle, Thomas Rohwetter, Nikita Gupta, George Avetian, Elisa Bladelli, Mariaelena Pierobon, Yu Chen, Qinggong Tang, Martin Schnermann, Olga Rodriguez, David Robbins, Terrence R Burke, Chris Albanese, Chukwuemeka Ihemelandu","doi":"10.1080/15384101.2024.2364578","DOIUrl":"10.1080/15384101.2024.2364578","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most common cancer worldwide. In the United States alone, CRC was responsible for approximately 52,550 deaths in 2023, with an estimated 153,020 new cases. CRC presents with synchronous peritoneal spread in 5-10% of patients, and up to 20-50% of patients with recurrent disease will develop metachronous colorectal cancer peritoneal metastatic (CRC-PM) disease. Eradication of the tumor, tumor margins and microscopic residual disease is paramount, as microscopic residual disease is associated with local recurrences, with 5-year survival rates of less than 35%. The success of resection and reduction of residual disease depends on the accuracy with which cancer cells and normal tissue can be intra-operatively distinguished. Fluorescence Molecular Imaging (IFMI) and tumor-targeted contrast agents represent a promising approach for intraoperative detection and surgical intervention. Proper target selection, the development of scalable imaging agents and enhanced real-time tumor and tumor microenvironment imaging are critical to enabling enhanced surgical resection. LGR5 (leucine-rich repeat-containing G-protein-coupled receptor 5), a colonic crypt stem cell marker and the receptor for the R-spondins (RSPO) in the Wnt signaling pathway, is also expressed on colorectal cancer stem cells (CSC) and on CRC tumors and metastases, suggesting it could be a useful target for imaging of CRC. However, there are numerous diverging reports on the role of LGR5 in CRC therapy and outcomes. Herein, we report on the synthesis and validation of a 37 amino acid RSPO1-mimetic peptide, termed RC18, that was specifically designed to access the R-spondin binding site of LGR5 to potentially be used for interoperative imaging of CRC-PM. The receptor-binding capabilities of the RC18 indicate that direct interactions with LGR5 neither significantly increased LGR5 signaling nor blocked RSPO1 binding and signal transduction, suggesting that the RSPO1-mimetic is functionally inert, making it an attractive contrast agent for intraoperative CRC-PM imaging.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-12"},"PeriodicalIF":3.4,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction: Cdc25C/cdc2/cyclin B, raf/MEK/ERK and PERK/eIF2α/CHOP pathways are involved in forskolin-induced growth inhibition of MM.1S cells by G2/M arrest and mitochondrion-dependent apoptosis.","authors":"","doi":"10.1080/15384101.2024.2370720","DOIUrl":"https://doi.org/10.1080/15384101.2024.2370720","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction: miR-96-5p regulated TGF-β/SMAD signaling pathway and suppressed endometrial cell viability and migration via targeting TGFBR1.","authors":"","doi":"10.1080/15384101.2024.2370717","DOIUrl":"https://doi.org/10.1080/15384101.2024.2370717","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression.","authors":"","doi":"10.1080/15384101.2024.2370712","DOIUrl":"https://doi.org/10.1080/15384101.2024.2370712","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statement of Retraction: Hsa-miR-425-5p promotes tumor growth and metastasis by activating the CTNND1-mediated β-catenin pathway and EMT in colorectal cancer.","authors":"","doi":"10.1080/15384101.2024.2370718","DOIUrl":"https://doi.org/10.1080/15384101.2024.2370718","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1"},"PeriodicalIF":3.4,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}