Cell and Bioscience最新文献

{"title":"The indispensable role of Mediator complex subunit 27 during neurodevelopment.","authors":"Xiaocheng Li, Nuermila Yiliyaer, Tianyu Guo, Hui Zhao, Yong Lei, Shen Gu","doi":"10.1186/s13578-025-01425-7","DOIUrl":"10.1186/s13578-025-01425-7","url":null,"abstract":"<p><strong>Background: </strong>MED27 is a subunit of the Mediator complex, a highly conserved protein assembly that initiates transcription by bridging transcription factors bound at enhancers to RNA polymerase II transcription machinery at promoters. Recently, we identified an autosomal recessive neurodevelopmental disorder (NDD) caused by loss-of-function (LoF) variants in the MED27 gene. Affected individuals exhibit global developmental delay, intellectual disability, dystonia, and cerebellar atrophy, highlighting the neuronal system's vulnerability to MED27 disruptions.</p><p><strong>Results: </strong>To investigate the pathogenicity mechanisms and essential roles of this gene during neurodevelopment, we generated multiple zebrafish lines with LoF mutations in med27. Homozygous mutant zebrafish displayed severe developmental defects, motor deficits, and cerebellar atrophy, recapitulating the clinical phenotypes observed in MED27-NDD patients. Rescue experiments revealed that patient-specific mutant MED27 mRNA failed to restore normal phenotypes in mutant zebrafish, unlike wildtype MED27 mRNA, underscoring the clinical relevance of our models. Molecular analysis identified transcription factors foxo3a and fosab as direct downstream targets of med27. These genes are well-established master regulators in the central nervous system, providing mechanistic insights into how med27 disruption impairs neuronal and cerebellar development.</p><p><strong>Conclusion: </strong>Our findings establish med27 as a critical gene of embryogenesis and neurogenesis, shedding light on the disease mechanism underlying MED27-associated NDDs.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"83"},"PeriodicalIF":6.1,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alpha fetoprotein (AFP)-producing gastric cancer: clinicopathological features and treatment strategies.","authors":"Bixian Luo, Zelai Wu, Chengyu Hu, Weixun Xie, Jun He, Hongming Liu, Dong Cao, Yong Liu, Yuxin Zhong, Weihua Gong","doi":"10.1186/s13578-025-01424-8","DOIUrl":"10.1186/s13578-025-01424-8","url":null,"abstract":"<p><p>Alpha-fetoprotein (AFP) is a widely recognized tumor marker for hepatocellular carcinoma and yolk sac tumors. Alpha-fetoprotein-producing gastric cancer (AFPGC) is a rare but highly malignant subtype of gastric cancer associated with poor prognosis. It is characterized by AFP positivity detected in serum or immunohistochemical staining, may along with hepatocellular differentiation. In recent years, advancements in molecular biology and therapeutic agents have led to a deeper understanding of AFPGC. However, the mechanisms underlying its tumorigenesis and invasive metastasis remain unclear. This article summarizes the traits of AFP, its clinicopathological features, and therapeutic strategies for AFP-positive gastric cancer, providing a better understanding and reference for the clinical diagnosis and treatment of AFPGC.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"82"},"PeriodicalIF":6.1,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.","authors":"Lukáš Čajánek, Sindija Smite, Olha Ivashchenko, Martina Huranova","doi":"10.1186/s13578-025-01403-z","DOIUrl":"10.1186/s13578-025-01403-z","url":null,"abstract":"<p><p>Cilia are versatile, microtubule-based organelles that facilitate cellular signaling, motility, and environmental sensing in eukaryotic cells. These dynamic structures act as hubs for key developmental signaling pathways, while their assembly and disassembly are intricately regulated along cell cycle transitions. Recent findings show that factors regulating ciliogenesis and cilia dynamics often integrate their roles across other cellular processes, including cell cycle regulation, cytoskeletal organization, and intracellular trafficking, ensuring multilevel crosstalk of mechanisms controlling organogenesis. Disruptions in these shared regulators lead to broad defects associated with both ciliopathies and cancer. This review explores the crosstalk of regulatory mechanisms governing cilia assembly, disassembly, and maintenance during ciliary signaling and the cell cycle, along with the broader implications for development, tissue homeostasis, and disease.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"81"},"PeriodicalIF":6.1,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alkylglycerol monooxygenase represses prostanoid biosynthesis in a sex-dependent manner.","authors":"Zhigang Rao, Katharina Lackner, Ilaria Dorigatti, Natascha Brigo, Denise Kummer, Minh Bui Hoang, Christa Pfeifhofer-Obermair, Günter Weiss, Ernst R Werner, Andreas Koeberle, Katrin Watschinger","doi":"10.1186/s13578-025-01419-5","DOIUrl":"10.1186/s13578-025-01419-5","url":null,"abstract":"<p><strong>Background: </strong>Ether lipids are important constituents of biological membranes and harbor fatty alcohols attached via ether linkages to the sn-1 position of the glycerol backbone. Depending on the nature of the ether bond, they are subdivided into 1-O-alkyl (plasmanyl) and 1-O-alk-1'-enyl (plasmenyl) subclasses. They often contain polyunsaturated fatty acids at the sn-2 position, implicating them in cellular signaling and inflammatory processes including lipid mediator biosynthesis. Lipid mediators are produced by immune and non-immune cells, have diverse homeostatic and immunoregulatory functions and, together with other factors, orchestrate the initiation and resolution of inflammation. To date, alkylglycerol monooxygenase is the only known enzyme capable of cleaving alkylglycerols, one of two ether lipid subclasses. However, the exact role of alkylglycerol monooxygenase and that of its substrates in lipid mediator biosynthesis remains unclear.</p><p><strong>Results: </strong>Using a knockout mouse model, we demonstrate a sex- and cell type-dependent role of alkylglycerol monooxygenase in limiting prostanoid formation without affecting polyunsaturated fatty acid release, as revealed by metabololipidomics profiling of lipid mediators using ultra-performance liquid chromatography‒tandem mass spectrometry. This female-specific effect is driven by the suppression of prostaglandin G/H synthase 2 transcription, as deficiency in alkylglycerol monooxygenase significantly elevated prostaglandin G/H synthase 2 gene expression in female bone marrow-derived macrophages of the M1 phenotype. Furthermore, this regulatory role of alkylglycerol monooxygenase extends to visceral white adipose tissue, where elevated prostaglandin G/H synthase 2 expression and enhanced prostaglandin E₂ production were observed in female samples following alkylglycerol monooxygenase knockout.</p><p><strong>Conclusion: </strong>Our results expand the immunomodulatory functions of ether lipid metabolism and highlight the sex- and cell type-dependent role of alkylglycerol monooxygenase in controlling lipid mediator production and maintaining tissue homeostasis.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"80"},"PeriodicalIF":6.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-translational modifications in the pathophysiological process of metabolic dysfunction‑associated steatotic liver disease.","authors":"Yiyang Min, Yiqiao Zhang, Yu Ji, Shanshan Liu, Chengjian Guan, Luyang Wei, Huajing Yu, Zhongtao Zhang","doi":"10.1186/s13578-025-01411-z","DOIUrl":"10.1186/s13578-025-01411-z","url":null,"abstract":"<p><p>In recent years, the prevalence of metabolic dysfunction‑associated steatotic liver disease (MASLD), which was called non-alcoholic fatty liver disease (NAFLD), has been progressively increasing in populations. The progression of MASLD encompasses a spectrum from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and ultimately to cirrhosis or even hepatocellular carcinoma. During the early stages of the disease, lipid accumulation and endoplasmic reticulum stress may lead to abnormalities in hepatic DNA expression, protein synthesis, and post-translational modifications (PTMs). PTMs play a crucial role in the progression of MASLD and include histone and non-histone modifications, with major types including methylation, acetylation, ubiquitination, and phosphorylation. Numerous studies indicate that within MASLD-related signaling pathways, PTMs can modulate protein activity, localization, folding, and interactions by altering their physicochemical properties. This review summarizes various significant PTMs involved in MASLD progression to elucidate the regulatory mechanisms and pathogenesis associated with the disease.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"79"},"PeriodicalIF":6.1,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WNT3 promotes chemoresistance to oxaliplatin in oral squamous cell carcinoma via regulating ABCG2 expression.","authors":"Kairui Sun, Xuyang Zhang, Ruihuan Gan, Shuoqi Lin, Yu Chen, Dali Zheng, Youguang Lu","doi":"10.1186/s13578-025-01414-w","DOIUrl":"10.1186/s13578-025-01414-w","url":null,"abstract":"<p><p>Oxaliplatin (OXA) is a frontline therapeutic agent used in the treatment of oral squamous cell carcinoma (OSCC). However, the development of chemoresistance has emerged as a significant challenge, compromising the effectiveness of treatment strategies. Therefore, there is a critical need to unravel the mechanisms underpinning drug resistance and to identify potential therapeutic targets. In recent years, there has been a growing interest in understanding the role of drug efflux in cancer chemoresistance mechanisms. Despite this, the contribution of ABCG2, a member of the ATP-binding cassette (ABC) transporter family, to oxaliplatin resistance in OSCC remains unclear. In the current study, we aimed to investigate the involvement of ABCG2 in oxaliplatin resistance in OSCC and to elucidate the molecular mechanisms through which the Wingless and Int-1 (WNT) canonical signaling pathway upregulates ABCG2 to promote chemoresistance. To achieve this, we established oxaliplatin-resistant (OXA-R) OSCC cells as a model system. Our investigations revealed that the efflux ability of resistant cells was enhanced and the ABCG2 expression was up-regulated. Genetic silencing of ABCG2 significantly attenuated both efflux activity and chemoresistance in these resistant cells. Notably, we observed aberrant activation of the WNT canonical signaling pathway in resistant cells, accompanied by heightened expression of the WNT3 ligand. Additionally, overexpression of WNT3 in parental cells recapitulated the activation of the WNT canonical signaling cascade, resulting in increased chemoresistance, enhanced efflux function, and elevated ABCG2 expression levels. Conversely, inhibition of WNT3 in resistant cells resulted in reduced chemoresistance, suppression of efflux activity, and decreased ABCG2 expression. Finally, treatment with the WNT/β-catenin pathway inhibitor methyl 3-benzoate (MSAB) effectively reversed chemoresistance in resistant cells. Mechanistically, our studies revealed that the abnormal activation of the WNT canonical pathway promotes the recruitment of the transcription factor lymphoid enhancer-binding factor 1 (LEF1) to the ABCG2 promoter, thereby enhancing its transcriptional activity. In summary, our findings underscore the critical role of WNT3-mediated activation of the WNT canonical signaling pathway in upregulating ABCG2 expression, which enhances oxaliplatin efflux and contributes to the development of oxaliplatin resistance in OSCC.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"77"},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Domain acquisition enabled functional expansion of the TFIIS transcription factor family.","authors":"Kateryna Matveyeva, Ainhoa Sánchez de Diego, María Ángeles García-López, Julio Gutiérrez, Thierry Fischer, Karel H M van Wely","doi":"10.1186/s13578-025-01423-9","DOIUrl":"10.1186/s13578-025-01423-9","url":null,"abstract":"<p><p>TFIIS and its homologs were long considered a delimited family of transcription factors, for the ability to induce RNA Polymerase II backtracking and nascent RNA cleavage. Recent studies however show that the relevant domains, which correspond to the TFIIS middle and carboxyterminal regions, are used to control transcription by additional protein architectures. The TFIIS middle region is paired with a SPOC domain in BYE1, the founder protein of the subfamily, and in its homologs; this combination of domains accommodates additional features such as a small zinc finger resembling the TFIIS carboxyterminal region. In metazoans, the architecture has evolved additional extensions to act on downstream RNA processing. Here, we argue in favor of a single protein superfamily encompassing TFIIS, BYE1, and their metazoan homologs. We conclude that the TFIIS middle domain comprises a common Pol2-interacting domain, shared by various generic protein functions. Domain composition of the vertebrate BYE1 homologs indicates a role in transcription elongation. Depending on the combination with other structures, the TFIIS middle domain may promote mutually exclusive activities, for example backtracking versus RNA synthesis and splicing. In this way, exchange of TFIIS for other superfamily members supports the separate Pol2 actions.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"78"},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism and application of lactylation in cancers.","authors":"Jiewen Wang, Mingjing Peng, Linda Oyang, Mengzhou Shen, Shizhen Li, Xianjie Jiang, Zongyao Ren, Qiu Peng, Xuemeng Xu, Shiming Tan, Longzheng Xia, Wenjuan Yang, Haofan Li, Nayiyuan Wu, Yanyan Tang, Jinguan Lin, Qianjin Liao, Yaqian Han, Yujuan Zhou","doi":"10.1186/s13578-025-01415-9","DOIUrl":"10.1186/s13578-025-01415-9","url":null,"abstract":"<p><p>Lactate is a crucial product of cancer metabolism, creating an acidic environment that supports cancer growth and acts as a substrate for lactylation. Lactylation, a newly discovered epigenetic modification, plays a vital role in cancer cell signaling, metabolic reprogramming, immune response, and other functions. This review explores the regulation of lactylation, summarizes recent research on its role in cancers, and highlights its application in cancer drug resistance and immunotherapy. These insights aim to provide new avenues for targeting lactylation in cancer therapy.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"76"},"PeriodicalIF":6.1,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linear ubiquitination of p31^comet by HOIP couples cytokine response with mitotic regulation.","authors":"Yifeng Gao, Qing Yin, Yaser Gamallat, Michael G Grant, Aidan H Snell, Xingxing Shi, Lara N Ulstad, Arshita Singh, Tingan Chen, Joseph O Johnson, Dorina Avram, Lixin Wan","doi":"10.1186/s13578-025-01416-8","DOIUrl":"10.1186/s13578-025-01416-8","url":null,"abstract":"<p><strong>Background: </strong>Inflammation and genomic instability are among the hallmarks of human cancer. Proinflammatory cytokines induce DNA damage through the accumulation of reactive oxygen and nitrogen species (RONS), which often leads to base alternations. The link between proinflammatory cytokines and chromosomal instability remains largely elusive.</p><p><strong>Results: </strong>Here, we report that the mitotic checkpoint protein p31^comet (MAD2L1BP) is modified by linear ubiquitination via the E3 ubiquitin ligase HOIP after cytokine stimulation. HOIP-mediated polyubiquitination of p31^comet occurs on its C-terminal lysine residues. Ubiquitinated p31^comet displays reduced binding to PLK1, which phosphorylates and inactivates p31^comet. Thus HOIP positively  regulates p31^comet function. Consistent with this notion, HOIP-deficient cells exhibit prolonged mitotic duration similar to p31^comet knockout. Mitotic defects are also more prevalent in cells without HOIP or p31^comet. Moreover, compared with the cells expressing wild-type p31^comet, cells expressing a ubiquitination-deficient p31^comet mutant take more time to complete the M phase.</p><p><strong>Conclusions: </strong>Our results together uncover a mechanistic link between the proinflammatory cytokines and the mitotic checkpoint pathways. This molecular switch could be explored as a potential therapeutic target in inflammation-driving or p31^comet overexpressed cancer types.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"75"},"PeriodicalIF":6.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel roles for CREG1 in hematopoiesis revealed by single-cell RNA sequencing.","authors":"Xiao Han, Keliang Pang, Xiaohui Liu, Jun Zhou, Jun Zhu, Hao Yuan","doi":"10.1186/s13578-025-01407-9","DOIUrl":"10.1186/s13578-025-01407-9","url":null,"abstract":"<p><strong>Background: </strong>Hematopoiesis, the process of generating diverse blood cell lineages, is essential for maintaining organismal homeostasis and survival. CREG1 has been implicated in various cellular processes, including proliferation, differentiation, and senescence. However, its role in adult hematopoiesis and the development of specific blood cell lineages remains largely unknown.</p><p><strong>Results: </strong>In this study, we utilized single-cell RNA sequencing (scRNA-seq) to investigate the function of CREG1 in hematopoietic development in adult zebrafish. Our analysis revealed significant alterations in cellular composition and gene expression profiles in kidney marrow of creg1-deficient zebrafish, particularly affecting B cell, T/NK cell, and erythroid cell development. The loss of CREG1 led to impaired endocytosis and lysosomal activity in lymphocytes, and inhibited differentiation of classical erythroid cells while promoting the development of immune-associated erythroid cells. These findings highlight a critical role for CREG1 in regulating hematopoietic lineage development, potentially through modulation of cell survival, endocytosis, and lysosomal function.</p><p><strong>Conclusions: </strong>Our study expands the current understanding of CREG1's role in hematopoiesis and provides a foundation for future investigations into the specific molecular mechanisms by which CREG1 regulates hematopoietic lineage development and function.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"74"},"PeriodicalIF":6.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}