Cell Cycle最新文献

{"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":"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":"779-795"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184135/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid hormone enhances estrogen-mediated proliferation and cell cycle regulatory pathways in steroid receptor-positive breast Cancer.","authors":"Reema S Wahdan-Alaswad, Susan M Edgerton, Hyun Min Kim, Aik Choon Tan, Bryan R Haugen, Bolin Liu, Ann D Thor","doi":"10.1080/15384101.2023.2249702","DOIUrl":"10.1080/15384101.2023.2249702","url":null,"abstract":"<p><p>Estrogen receptor (ER) α expression and associated signaling is a major driver of over two-thirds of all breast cancers (BC). ER targeting strategies are typically used as a first-line therapy in patients with steroid receptor positive (SR+) disease. Secondary resistance to anti-estrogenic agents may occur with clonal expansion and disease progression. Mechanisms underlying hormone resistance are an expanding field of significant translational importance. Cross-talk with other nuclear hormones, receptors, and signaling pathways, including thyroid hormones (TH) and their receptors (THRs), have been shown to promote endocrine therapy resistance in some studies. We have shown that TH replacement therapy (THRT) was independently and significantly associated with higher rates of relapse and mortality in SR positive (+), node-negative (LN-) BC patients, whereas it showed no association with outcomes in SR negative (-) patients. LN-, SR+ patients receiving THRT and tamoxifen had the worst outcomes, suggesting a pro-carcinogenic interaction that significantly and independently shortened survival and increased mortality. Using <i>in vivo</i> and <i>in vitro</i> models, we previously showed hormonal cross-talk, altered gene signaling, target gene activation, and resistance to tamoxifen in the presence of TH. In this report, we show TH ± E2 ± tamoxifen inhibits cell cycle control signaling, reduces apoptosis, and enhances cell proliferation, tumor growth, tamoxifen resistance, and clonal expansion. Mechanistically these changes involve numerous genes and pathways, including critical cell cycle regulatory proteins and genes identified using various molecular methods. These studies facilitate a greater mechanistic understanding of the biological and molecular impact of TH on SR+ BC.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"747-766"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10314655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","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":"796-816"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184169/pdf/","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":"OA","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":"767-778"},"PeriodicalIF":3.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184107/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of key miRNAs and a microRNA-mRNA regulatory network associated with liver cancer","authors":"Jie Tang, Song Li, Zixiao Zhou, Weicai Chang, Yongqiang Wang, Juan Mei, Shaobo Zhou","doi":"10.1080/15384101.2024.2335024","DOIUrl":"https://doi.org/10.1080/15384101.2024.2335024","url":null,"abstract":"MiRNAs play crucial regulatory roles in the growth and development of tumor cells by serving as carriers of post-transcriptional regulatory information derived from genes. Investigating the potenti...","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"44 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140314421","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":"Effects of Ninjurin 2 polymorphisms on susceptibility to coronary heart disease","authors":"Yuping Yan, Xiaoyan Du, Xia Dou, Jingjie Li, Wenjie Zhang, Shuangyu Yang, Wenting Meng, Gang Tian","doi":"10.1080/15384101.2024.2330225","DOIUrl":"https://doi.org/10.1080/15384101.2024.2330225","url":null,"abstract":"The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD).We conducted a case-control study with 499 CHD cases and 505 a...","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"158 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140204677","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":"Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A","authors":"Michał Wójcik, Nikola Zmarzły, Alicja Derkacz, Tomasz Kulpok-Bagiński, Natasza Blek, Beniamin Oskar Grabarek","doi":"10.1080/15384101.2024.2320508","DOIUrl":"https://doi.org/10.1080/15384101.2024.2320508","url":null,"abstract":"Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes e...","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":"56 1","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140070744","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":"Evaluation of differences in expression pattern of three isoforms of the transforming growth factor beta in patients with lumbosacral stenosis.","authors":"Dawid Sobański, Paweł Bogdał, Rafał Staszkiewicz, Małgorzata Sobańska, Michał Filipowicz, Ryszard Adam Czepko, Damian Strojny, Beniamin Oskar Grabarek","doi":"10.1080/15384101.2024.2345484","DOIUrl":"10.1080/15384101.2024.2345484","url":null,"abstract":"<p><p>The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-β-1-3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of <i>TGF-β-1</i> and <i>TGF-β-3</i>, while <i>TGF-β-2</i> increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-β-1, TGF-β-2, and TGF-β-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-β-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; <i>p</i> < 0.0001), TGF-β-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; <i>p</i> < 0.0001), TGF-β-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, <i>p</i> < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-β-1-3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-β-1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-β isoforms level for better understanding and managing degenerative spinal conditions.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"555-572"},"PeriodicalIF":4.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11135850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the multifaceted role of RASGRP1 in disease: immune, neural, metabolic, and oncogenic perspectives.","authors":"Shangzhi Fan, Bo Kang, Shaoqian Li, Weiyi Li, Canyu Chen, Jixiang Chen, Lijing Deng, Danjun Chen, Jiecan Zhou","doi":"10.1080/15384101.2024.2366009","DOIUrl":"10.1080/15384101.2024.2366009","url":null,"abstract":"<p><p>RAS guanyl releasing protein 1 (RASGRP1) is a guanine nucleotide exchange factor (GEF) characterized by the presence of a RAS superfamily GEF domain. It functions as a diacylglycerol (DAG)-regulated nucleotide exchange factor, specifically activating RAS through the exchange of bound GDP for GTP. Activation of RAS by RASGRP1 has a wide range of downstream effects at the cellular level. Thus, it is not surprising that many diseases are associated with RASGRP1 disorders. Here, we present an overview of the structure and function of RASGRP1, its crucial role in the development, expression, and regulation of immune cells, and its involvement in various signaling pathways. This review comprehensively explores the relationship between RASGRP1 and various diseases, elucidates the underlying molecular mechanisms of RASGRP1 in each disease, and identifies potential therapeutic targets. This study provides novel insights into the role of RASGRP1 in insulin secretion and highlights its potential as a therapeutic target for diabetes. The limitations and challenges associated with studying RASGRP1 in disease are also discussed.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"722-746"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_0050444 represses esophageal squamous cell carcinoma progression through sponging miR-486-3p to upregulate C10orf91.","authors":"Dongli Zhang, Yan Zhou, Chenyang Jiao, Hongfang Kong, Zhibin Zhao, Yujiang Li","doi":"10.1080/15384101.2024.2357909","DOIUrl":"10.1080/15384101.2024.2357909","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) ranks as the fourth leading cause of tumor-related deaths in China. Circ_0050444 has been revealed to be downregulated in ESCC tissues, however, its function and molecular mechanism underlying ESCC progression is unknown. Therefore, we attempted to clarify the functional role and molecular mechanism of circ_0050444 underlying ESCC progression. RT-qPCR and RNase R digestion assays were used to evaluate circ_0050444 expression and stability characteristics in ESCC cells. Gain-of-function assays were conducted to clarify circ_0050444 role in ESCC cell malignant behaviors. Bioinformatics and mechanism experiments were performed to assess the relationship between circ_0050444 or C10orf91 and miR-486-3p in ESCC cells. Rescue assays were conducted to evaluate the regulatory function of the circ_0050444-miR-486-3p-C10orf91 axis in ESCC cellular processes. Circ_0050444 expression was found to be downregulated both in ESCC patient tissues and cell lines. Functionally, circ_0050444 overexpression repressed ESCC cell proliferative, migratory, and invasive capabilities in cultured cells. Mechanistically, circ_0050444 was found to be competitively bound with miR-486-3p to upregulate C10orf91 in ESCC cells. Moreover, the impact of circ_0050444 elevation on ESCC cell proliferation, migration, and invasion was countervailed by C10orf91 silencing. Circ_0050444 presents downregulation and functions as a tumor suppressor in ESCC progression. Circ_0050444 suppresses ESCC proliferation, migration, and invasion through sponging miR-486-3p to upregulate C10orf91, providing a potential new direction for seeking therapeutic plans for ESCC.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"693-702"},"PeriodicalIF":3.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}