Cell Proliferation最新文献

{"title":"Glutaminase-1 Mediated Glutaminolysis to Glutathione Synthesis Maintains Redox Homeostasis and Modulates Ferroptosis Sensitivity in Cancer Cells.","authors":"Changsen Bai, Jialei Hua, Donghua Meng, Yue Xu, Benfu Zhong, Miao Liu, Zhaosong Wang, Wei Zhou, Liming Liu, Hailong Wang, Yang Liu, Lifang Li, Xiuju Chen, Yueguo Li","doi":"10.1111/cpr.70036","DOIUrl":"https://doi.org/10.1111/cpr.70036","url":null,"abstract":"<p><p>Glutaminase-1 (GLS1) has garnered considerable interest as a metabolic target in cancer due to its heightened involvement and activity. However, the precise fate of glutaminolysis catalysed by GLS1 in cancer cells remains elusive. We found that GLS1 knockout led to significant suppression of cancer cell proliferation, which can be reversed or partially restored by supplementation of glutamate or non-essential amino acids that can be converted into glutamate. The addition of spliceosomal KGA or GAC ameliorates cancer cell growth in vitro and in vivo, providing both simultaneously completely reverse the effect. The primary metabolic fate of glutamate produced through glutaminolysis in cancer cells is mainly used to produce glutathione (GSH) for redox homeostasis, not entering the tricarboxylic acid cycle or synthesising nucleotides. GSH monoethyl ester (GSH-MEE) effectively rescues the inhibition of cancer cell proliferation caused by GLS1 knockout. Deletion of GLS1 results in an elevation of reactive oxygen species (ROS) and malondialdehyde (MDA), a reduction of NADPH/NADP⁺ ratio, and an augmented susceptibility of cells to ferroptosis. Glutathione Peroxidase 4 (GPX4) and GPX1 exhibit complementary roles in redox regulation, with GLS1 knockout promoting GPX4 degradation. Pharmacological inhibition of GLS1 synergises with GPX4 inhibitor to suppress tumour growth. Dual targeting of GPX4 and GPX1 presents a potent anti-cancer strategy. This metabolic mechanism facilitates a deeper comprehension of the abnormal glutamine metabolism in cancer cells, establishing a theoretical basis for the potential clinical utilisation of GLS1 inhibitors and presenting novel perspectives for advancing combinatorial therapeutic approaches.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70036"},"PeriodicalIF":5.9,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976063","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":"Inhibition of Alkbh5 Attenuates Lipopolysaccharide-Induced Lung Injury by Promoting Ccl1 m6A and Treg Recruitment.","authors":"Hongdou Ding, Xinnan Xu, Yaoyao Zhu, Xinyu Ling, Li Xu","doi":"10.1111/cpr.70032","DOIUrl":"https://doi.org/10.1111/cpr.70032","url":null,"abstract":"<p><p>This paper discussed the role of AlkB homologue 5 (Alkbh5) in the progression of lipopolysaccharide (LPS)-induced acute lung injury (ALI). LPS-induced ALI models were established in Alkbh5 knockout (KO) and knock-in (KI) mice. The m6A levels in lung tissues were analysed using m6A dot assays. The lung injury was analysed by determining ALI-related markers and histological staining. Mouse MLE12 cells were exposed to LPS for in vitro experiments, and the influence of Alkbh5 on cell viability, apoptosis and reactive oxygen species (ROS) production was analysed. RNA-seq analysis was performed to analyse gene changes upon Alkbh5 deficiency. Functions of the Alkbh5-C-C motif chemokine ligand 1 (Ccl1) cascade in ALI were further verified using the Alkbh5 antagonist DDO-2728 and a recombinant protein of Ccl1 (mCcl1). Alkbh5 was upregulated in lung tissues following LPS exposure. Alkbh5 knockout in mice mitigated LPS-induced lung injury, as indicated by reduced serum levels of lung injury markers and reduced immune cell infiltration, fibrosis and apoptosis. Conversely, Alkbh5 overexpression in mice resulted in reverse trends. In vitro, Alkbh5 knockdown in MLE12 cells enhanced cell viability while reducing cell apoptosis and ROS production. Mechanistically, Alkbh5 was found to bind to and destabilise Ccl1 mRNA, leading to increased Treg recruitment. Treatment with DDO-2728 or mCcl1 in mice increased Treg infiltration, thus improving lung tissue pathology and reducing lung injury. This study suggests that Alkbh5 is implicated in ALI progression by reducing Ccl1-mediated Treg recruitment, making it a promising target for ALI management.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70032"},"PeriodicalIF":5.9,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987315","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":"IMPDH2's Central Role in Cellular Growth and Diseases: A Potential Therapeutic Target.","authors":"Zheng Li, Yunpeng Zou, Jiayao Niu, Ying Zhang, Aohua Yang, Wenyu Lin, Jie Guo, Shuya Wang, Ronghan Liu","doi":"10.1111/cpr.70031","DOIUrl":"https://doi.org/10.1111/cpr.70031","url":null,"abstract":"<p><p>IMPDH2 is a rate-limiting enzyme in guanine nucleotide biosynthesis. It plays diverse roles in various physiological and pathological processes: nucleotide metabolism, inflammation, immune function, ribosomal stress. Structural or regulatory alterations in IMPDH2 are linked to significant health issues, and critical relevance in disease progression. We aim to underscore the potential of IMPDH2 as a promising therapeutic target for clinical applications.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70031"},"PeriodicalIF":5.9,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980549","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":"Deciphering Sequence Determinants of Zygotic Genome Activation Genes: Insights From Machine Learning and the ZGAExplorer Platform.","authors":"Jixiang Xing, Siqi Yang, Yuchao Liang, Pengwei Hu, Bingjie Dai, Hanshuang Li, Yongqiang Xing, Yongchun Zuo","doi":"10.1111/cpr.70039","DOIUrl":"https://doi.org/10.1111/cpr.70039","url":null,"abstract":"<p><p>The mammalian life cycle initiates with the transition of genetic control from the maternal to the embryonic genome during zygotic genome activation (ZGA), which becomes pivotal for development. Nevertheless, understanding the conservation of genes and transcription factors (TFs) that underlie mammalian ZGA remains limited. Here, we compiled a comprehensive set of ZGA genes from mice, humans, pigs, bovines and goats, including Nr5a2 and TPRX1/2. The identification of 111 homologous genes through comparative analyses was followed by the discovery of a conserved genetic coding region, suggesting potential sequence preferences for ZGA genes. Notably, an interpretable machine learning model based on k-mer core features showed excellent performance in predicting ZGA genes (area under the ROC curve [AUC] > 0.81), revealing abundant and intricate 6-base sequence specific patterns and potential binding TFs, including motifs from NR5A2 and TPRX1/2. Further analysis demonstrated that gene sequence features and epigenetic modification features play equally important roles in regulating ZGA genes. Ultimately, we developed the ZGAExplorer platform to provide an invaluable resource for screening ZGA genes. Our study unravels the sequence determinants of ZGA genes across species through multi-omics data integration and machine learning, yielding insights into ZGA regulatory mechanisms and embryonic developmental arrest.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70039"},"PeriodicalIF":5.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964764","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":"Revitalising Aging Oocytes: Echinacoside Restores Mitochondrial Function and Cellular Homeostasis Through Targeting GJA1/SIRT1 Pathway.","authors":"Liuqing Yang, Xinle Lai, Fangxuan Lin, Nan Shi, Xinya Xu, Heng Wang, Xiaotian Li, Dan Shen, Haimo Qian, Xin Jin, Jiayi Chen, Zhongwei Huang, Xing Duan, Qin Zhang","doi":"10.1111/cpr.70044","DOIUrl":"https://doi.org/10.1111/cpr.70044","url":null,"abstract":"<p><p>As maternal age increases, the decline in oocyte quality emerges as a critical factor contributing to reduced reproductive capacity, highlighting the urgent need for effective strategies to combat oocyte aging. This study investigated the protective effects and underlying mechanisms of Echinacoside (ECH) on aging oocytes. ECH significantly improved cytoskeletal stability and chromosomal integrity, as demonstrated by restored spindle morphology and reinforced F-actin structures, essential for meiotic progression. It also preserved mitochondrial function by restoring membrane potential and dynamics, reducing ROS levels, and downregulating the DNA damage marker γ-H2AX, thereby alleviating oxidative stress and enhancing genomic stability. Furthermore, ECH promoted cellular homeostasis through modulation of lipid metabolism, autophagy and lysosomal function. Transcriptomic analyses identified GJA1 as a pivotal mediator of ECH's effects, validated through molecular docking and bio-layer interferometry. Functional studies showed that inhibiting GJA1 significantly reduced ECH's ability to enhance first polar body extrusion rates, mitochondrial function and antioxidant capacity, validating the critical role of the GJA1/SIRT1 pathway in combating oocyte aging. This study provides novel insights into the mechanisms of oocyte rejuvenation and highlights ECH as a promising therapeutic candidate for addressing age-related reproductive challenges.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70044"},"PeriodicalIF":5.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981216","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":"Membraneless Organelles and Phase Separation in Tumours: Mechanisms and Prospects.","authors":"Hao Yang, Zhong Chu, Shuwen Han, Yuefen Pan","doi":"10.1111/cpr.70027","DOIUrl":"https://doi.org/10.1111/cpr.70027","url":null,"abstract":"<p><p>Membraneless organelles (MLOs) are a type of subcellular compartment structure discovered in eukaryotes in recent years. They are mainly formed through the liquid-liquid phase separation (LLPS) and aggregation of macromolecular substances such as proteins or nucleic acids in cells. When cells are stimulated, they initiate a series of stress responses including gene transcription, RNA metabolism, translation, protein modification and signal transduction to maintain homeostasis. The dysregulation of these cellular processes is a key event in the occurrence and development of cancer. This article provides an overview of the structure and function of membraneless organelles, as well as the mechanisms of phase separation, to summarise the latest research progress on phase separation in tumours. It focuses on the role and molecular mechanism of LLPS in the development of tumours, with the aim of providing new theoretical references for developing drug action targets and innovative treatment strategies.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70027"},"PeriodicalIF":5.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987317","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":"Lactate and Lactylation in AKI-to-CKD: Epigenetic Regulation and Therapeutic Opportunities.","authors":"Yi Hou, Dongwei Liu, Zuishuang Guo, Cien Wei, Fengyu Cao, Yue Xu, Qi Feng, Fengxun Liu","doi":"10.1111/cpr.70034","DOIUrl":"https://doi.org/10.1111/cpr.70034","url":null,"abstract":"<p><p>Lactate is not only a byproduct of glycolysis, but is also considered an energy source, gluconeogenic precursor, signalling molecule and protein modifier during the process of cellular metabolism. The discovery of lactylation reveals the multifaceted functions of lactate in cellular metabolism and opens new avenues for lactate-related research. Both lactate and lactylation have been implicated in regulating numerous biological processes, including tumour progression, ischemic-hypoxic injury, neurodevelopment and immune-related inflammation. The kidney plays a crucial role in regulating lactate metabolism, influencing lactate levels while also being regulated by lactate. Previous studies have demonstrated the importance of lactate in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease (CKD). This review explores the role of lactate and lactylation in these diseases, comparing the function and metabolic mechanisms of lactate in normal and diseased kidneys from the perspective of lactylation. The key regulatory roles of lactylation in different organs, multiple systems, various pathological states and underlying mechanisms in AKI-to-CKD progression are summarised. Moreover, potential therapeutic targets and future research directions for lactate and lactylation across multiple kidney diseases are identified.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70034"},"PeriodicalIF":5.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955348","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":"RNF187 Facilitates Proliferation and Migration of Human Spermatogonial Stem Cells Through WDR77 Polyubiquitination.","authors":"Haoyue Hu, Xiaoxue Xi, Bing Jiang, Kehan Wang, Tiantian Wu, Xia Chen, Yueshuai Guo, Tao Zhou, Xiaoyan Huang, Jun Yu, Tingting Gao, Yibo Wu, Bo Zheng","doi":"10.1111/cpr.70042","DOIUrl":"https://doi.org/10.1111/cpr.70042","url":null,"abstract":"<p><p>The E3 ubiquitin ligase RNF187, also known as RING domain AP1 coactivator-1, is a member of the RING finger family. RNF187 is indispensable for the proliferation and migration of GC-1 cells derived from mouse spermatogonia and GC-2 cells derived from spermatocytes. However, it remains unclear whether RNF187 plays a crucial role in the self-renewal and migration of human spermatogonial stem cells (SSCs). In this study, we observed a positive correlation between RNF187 expression and the proliferation and migration of human SSCs. Through co-immunoprecipitation and mass spectrometry analyses, we identified WD repeat-containing protein 77 (WDR77) as an interacting partner of RNF187. Specifically, RNF187 recognises the K118 site of WDR77 through lysine 48-linked polyubiquitination, subsequently mediating its degradation via the ubiquitin-proteasome system (UPS). Further studies have revealed that decreased expression of WDR77 diminishes the symmetric dimethylation at H4R3 (H4R3me2s) catalysed by its interacting protein, the arginine methyltransferase PRMT5. This, in turn, relieves the transcriptional repression of early growth response protein 1 (EGR1), a positive regulator for human SSC maintenance. In conclusion, this study has unveiled a pivotal role for RNF187 in the proliferation and migration of human SSCs. This may provide a promising strategy for addressing non-obstructive azoospermia (NOA) caused by SSC dysfunction.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70042"},"PeriodicalIF":5.9,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802627","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":"Production and Functional Verification of 8-Gene (GGTA1, CMAH, β4GalNT2, hCD46, hCD55, hCD59, hTBM, hCD39)-Edited Donor Pigs for Xenotransplantation.","authors":"Jiaoxiang Wang, Kaixiang Xu, Tao Liu, Heng Zhao, Muhammad Ameen Jamal, Gen Chen, Xiaoying Huo, Chang Yang, Deling Jiao, Taiyun Wei, Hanfei Huang, Hongfang Zhao, Jianxiong Guo, Fengchong Wang, Xiong Zhang, Kai Liu, Siming Qu, Gang Wang, Hui Guo, Gang Chen, Hong-Ye Zhao, Zhong Zeng, Kefeng Dou, Hong-Jiang Wei","doi":"10.1111/cpr.70028","DOIUrl":"https://doi.org/10.1111/cpr.70028","url":null,"abstract":"<p><p>Gene-edited (GE) pig-to-human xenotransplantation continues to make breakthroughs, but which kind of gene combination is suitable for organ-specific transplantation remains unclear. In this study, we utilised CRISPR/Cas9 gene editing technology, PiggyBac transposon system, and serial somatic cell cloning technology to develop GTKO/CMAHKO/β4GalNT2KO/hCD46/hCD55/hCD59/hCD39/hTBM 8 gene-edited cloned (GEC) donor pigs and performed pig-to-non-human primate (NHP) transplantation to evaluate the effectiveness of these GEC pigs. The 8-GEC pigs were obtained by recloning with a 33-day-old 8-GEC fetus with O blood type, which was generated after cell transfection, screening of cell colonies, and somatic cell cloning. Molecular identification at DNA, mRNA, and protein levels confirmed successful 8-gene editing. Three copies of transgenes were identified by droplet digital polymerase chain reaction and whole genome sequencing, which were inserted into the introns of pig RFTN1 and MYO10 genes, as well as the intergenic region between PRLR and LOC110257300 genes of these 8-GEC pigs. The 8-GEC pigs also exhibited the ability of germline transmission when mated with our previously generated 4-GEC male pigs. Moreover, antigen-antibody binding assay and complement-dependent cytotoxicity assay demonstrated that 8-gene editing effectively reduced the immune incompatibility and kidney xenograft from 8-GEC pigs survived for 15 and 17 days in two NHPs, respectively. Postoperatively, the recipient serum antibodies IgA, IgG and IgM, complements C3 and C4, coagulation indicators PT, APTT, TT and FIB, as well as most electrolytes and liver function indicators remained relatively stable. Serum creatinine was normal within 10 days post operation. However, the kidney xenograft developed active antibody-mediated rejection at necropsy, characterised by the deposition of antibodies IgG and IgM, as well as complements C4d, C3c and C5b-C9, infiltration of CD68⁺ macrophages, and micro-thrombotic embolism of glomerular capillaries, etc. In conclusion, we successfully developed fertile 8-GEC pigs, which effectively alleviated immune rejection and exerted life-supporting kidney function in the recipients.</p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70028"},"PeriodicalIF":5.9,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794612","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":"Mei Xu,&nbsp;Dian Gan,&nbsp;Xi-Yu Zhang,&nbsp;Xiao-Tao He,&nbsp;Rui Xin Wu,&nbsp;Yuan Yin,&nbsp;Rui Jin,&nbsp;Lin Li,&nbsp;Yu-Jie Tan,&nbsp;Fa-Ming Chen,&nbsp;Xuan Li,&nbsp;Bei-Min Tian","doi":"10.1111/cpr.70038","DOIUrl":"https://doi.org/10.1111/cpr.70038","url":null,"abstract":"<p>The cover image is based on the article <i>SLC30A4-AS1 Mediates the Senescence of Periodontal Ligament Stem Cells in Inflammatory Environments via the Alternative Splicing of TP53BP1</i> by Mei Xu et al., https://doi.org/10.1111/cpr.13778.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":"58 4","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cpr.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770325","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}