Cell and Bioscience最新文献

{"title":"Cytoskeleton disruption and plasma membrane damage determine methuosis of normal and malignant cells.","authors":"Bin Dong, Jing Xiao, Junqi Wang, Xinhao Song, Hui Ji, Jiurong Peng, Xinru Weng, Dawei Guo, Shanxiang Jiang, Xiuge Gao","doi":"10.1186/s13578-025-01441-7","DOIUrl":"10.1186/s13578-025-01441-7","url":null,"abstract":"<p><strong>Background: </strong>Methuosis represents a novel cell death modality characterized by catastrophic cytoplasmic vacuolization in normal and malignant cells. However, the critical role and the underlying mechanism of cytoskeleton and plasma membrane damage in methuotic cells are largely unknown.</p><p><strong>Results: </strong>We found that cytoskeleton protein F-actin, α-tubulin, β-tubulin and filamin A/B were disrupted in a reversible-dependent manner. In addition, RhoA-ROCK1 signaling pathway mediated cytoskeleton disruption in methuotic cells. Excessive cytoplasmic vacuolization triggered cellular plasma membrane damage and the release of damage associated molecular patterns (DAMPs), including lactate dehydrogenase (LDH), adenosine triphosphate (ATP) and calreticulin (CRT). Furthermore, at the end phase of methuotic cells, plasma membrane was damaged independent of pore-forming protein phosphorylation mixed lineage kinase domain-like (p-MLKL) and gasdermin D (GSDMD). Endosomal sorting complex required for transport (ESCRT)-III especially its subunit charged multivesicular body protein 3 (CHMP3) and charged multivesicular body protein 5 (CHMP5) negatively regulated excessive vacuolization-induced plasma membrane damage in cells undergoing methuosis.</p><p><strong>Conclusions: </strong>The critical role and potential mechanism of cytoskeleton and plasma membrane damage in methuotic cells are known, which would facilitate the employment of methuosis in life science and pharmacology.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"96"},"PeriodicalIF":6.1,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568029","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":"Cholesterol confers resistance to Apatinib-mediated ferroptosis in gastric cancer.","authors":"Zhiwei Li, Chenxin Liu, Minghao Wang, Riqing Wei, Ru Li, Kaihua Huang, Huayuan Liang, Guoxin Li, Liying Zhao","doi":"10.1186/s13578-025-01435-5","DOIUrl":"10.1186/s13578-025-01435-5","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"95"},"PeriodicalIF":6.1,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565432","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":"Genomic ncRNAs regulating mitochondrial function in neurodegeneration: a neglected clue in the complex etiopathogenesis of multiple sclerosis.","authors":"Nima Sanadgol, Mahedeh Samadi, Clara Voelz, Roghayeh Khalseh, Javad Amini, Cordian Beyer, Markus Kipp, Tim Clarner","doi":"10.1186/s13578-025-01438-2","DOIUrl":"10.1186/s13578-025-01438-2","url":null,"abstract":"<p><p>Multiple sclerosis (MS), the most prevalent myelinopathy with unclear etiology, involves mitochondrial dysfunction that critically contributes to oligodendrocyte damage and neurodegeneration. Recent interest has surged around the role of inflammatory non-coding RNAs (ncRNAs) in mitochondrial function, particularly in the context of neurodegenerative diseases (NDs), where neuroinflammation is a hallmark feature. This review highlights the collection and characterization of mitochondrial-related ncRNAs (MRncRNAs) that have been extensively studied in the context of NDs. Through a literature review, we identified 35 MRncRNAs (23 miRNAs, 8 LncRNAs, and 4 circRNAs) across Parkinson's disease (PD), Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD), and Huntington's disease (HD). Notably, the inflammatory miRNAs miR-34a and miR-146a were commonly dysregulated in both PD and AD, while in HD, only a single miRNA, miR-196a, was identified. As expected, due to the mitochondrial nature of PD, the majority of MRncRNAs (9 miRNAs, 8 lncRNAs, and 3 circRNAs) were associated with this disorder. Further bioinformatic analysis of MRmiRNAs revealed that miR-124-5p, -146a-3p, and -15b-3p target mitochondrial genes more than others, and mRNA of pro-apoptotic protein BCL2L11 is the most targeted. Notably, the link between these MRncRNAs and mitochondrial function in MS remains unidentified. By evaluating upregulated MS-related ncRNAs in patients and comparing them with identified MRncRNAs, we found nine overlapping miRNAs (miR-15b, miR-21, miR-27b, miR-34a, miR-124, miR-137, miR-146a, miR-155, and miR-92a) as well as two shared lncRNAs, MALAT1 and HOTAIR (called MS/MRncRNAs). Further bioinformatic analysis of MS/MRmiRNAs revealed that the autophagy pathway is the most involved. Six of these miRNAs are significantly involved in MR diseases. Notably, miR-34a-5p showed a connection to oligodendrocyte mitochondria, while miR-15b targeted two MR hub genes, SDHC and BCL2. Moreover, several hub proteins (HIF1A, STAT3, MAPK1, GSK3B) targeted by these miRNAs are well-known regulators of inflammatory pathways and mitochondrial homeostasis: These findings highlight the critical roles of ncRNAs in mitochondrial dysfunction and neurodegeneration, emphasizing the urgent need for experimental studies on MRmiRNAs, particularly in the context of MS and other myelinopathies.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"93"},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530671","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":"ZNF146 accelerates lung adenocarcinoma progression through MDM2/p53 and PHGDH/ferroptosis.","authors":"Junkan Zhu, Shencheng Ren, Yanjun Yi, Zhiyao Wu, Han Lin, Guangyao Shan, Xiaolong Huang, Binyang Pan, Zhengyang Hu, Qihai Sui, Cheng Zhan, Shuai Wang, Jiaqi Liang","doi":"10.1186/s13578-025-01433-7","DOIUrl":"10.1186/s13578-025-01433-7","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"94"},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144530672","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":"ebv-sisRNA-3 contributes to the formation of G4-associated R-loop upstream of EBV lytic replication origin in latently infected cells.","authors":"Bo Wang, Grace Tin Yun Chung, Yi Shuai, Man Wu, Danyang Ji, Raymond Wai Ming Lung, Yuk Yu Chan, Ming Ting Liu, Ee Ling Kong, Shin Yee Hui, Hei Man Leung, Qian Wu, Melissa Sue Ann Chan, Xin Wang, Guang Zhu, Kevin Y Yip, Chun Kit Kwok, Kwok Wai Lo, Chi Man Tsang","doi":"10.1186/s13578-025-01437-3","DOIUrl":"10.1186/s13578-025-01437-3","url":null,"abstract":"<p><strong>Background: </strong>In EBV-associated epithelial cancers, only a limited number of viral proteins are translated, while multiple EBV-encoded non-coding RNAs are expressed to minimize activation of the host's immune response. These non-coding RNAs have been shown to play regulatory roles in maintaining latency and promoting cancer progression while many aspects of them remain to be elucidated.</p><p><strong>Results: </strong>Here we revealed abundant expression of ebv-sisRNA-3, a novel EBV transcript in nasopharyngeal carcinoma and EBV-associated gastric cancer. This 5-7 kb non-polyA transcript is derived from RPMS1 intron and is partially complementary to LF3. We observed high expression level of ebv-sisRNA-3 in multiple EBV-positive cancer cells and clinical specimens, with accumulation in the cell nucleus. Notably, ebv-sisRNA-3 invades the double-strand DNA in trans upstream of lytic replication origin in EBV genome and leads to the formation of R-loop and G-quadruplex simultaneously in the latently EBV-infected epithelial cells. Additionally, we revealed the locations of R-loops within the EBV genome and identified endogenous G-quadruplexes near the EBER1 and EBNA1 promoters.</p><p><strong>Conclusions: </strong>In this study, we revealed and characterized a novel EBV transcript ebv-sisRNA-3 widely expressed in latently infected cells. The unique ebv-sisRNA-3-binding R-loop and G-quadruplex structures near lytic replication origin may play a significant role in EBV lytic replication.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"91"},"PeriodicalIF":6.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512654","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":"Single-cell and spatial analyses of the GDF family in tumors, with a focus on the prognostic and biological role of GDF15 in hepatocellular carcinoma.","authors":"Xiaoqian Feng, Qian Huai, Fumin Zhang, Wenkang Yuan, Xingyu Li, Zhuo Yu, Hao Zhang, Yaoling Zhu, Xu Zhang, Baole Tao, Ying Dai, Yishan Du","doi":"10.1186/s13578-025-01431-9","DOIUrl":"10.1186/s13578-025-01431-9","url":null,"abstract":"<p><p>Growth differentiation factors (GDFs) are a subfamily of the TGF-β superfamily whose expression increases in response to cellular stress and disease. Despite emerging cell- or animal-based evidence supporting an association between the GDF subfamily and cancer, systematic pan-cancer analyses of the GDF subfamily based on single-cell and spatial transcriptomes remains unavailable. In this study, we performed a comprehensive analysis of the GDF subfamily in 33 cancers, including expression, diagnosis, methylation, prognostic value, immune infiltration analysis, and potential biological pathways. We focused on the analysis of multi-group scRNA-seq and spatial data in hepatocellular carcinoma (HCC) to determine the role of the GDF family in the tumor microenvironment and its applicability in immunotherapy. Moreover, both the gain and loss of function strategies were used to assess the function of Growth differentiation factor 15 (GDF15) in cell lines of HCC. The GDF subfamily is expressed to varying degrees in most tumors and is significantly correlated with the prognosis of cancer patients. Subsequent scRNA-seq analysis depicted the heterogeneous cellular ecosystems of normal liver and HCC. Hepatocytes expressing GDF15 were less differentiated in HCC, and GDF15 promoted proliferation and invasion of HCC cell lines. Compared to normal liver, the strength of crosstalk between GDF15-positive Hepatocytes and other cells was enhanced in tumors, especially cancer-associated fibroblasts (CAFs)-derived Periostin and GDF15-positive Hepatocytes both regulate each other and jointly promote hepatocarcinogenesis. Further spatial transcriptomic data showed that GDF15 expression was negatively correlated with immune infiltration, especially in M1-type macrophages. Notably, validation analyses in bulk RNA-seq consistently emphasized the clinical significance of these findings. This study provides a comprehensive overview of the oncogenic role of the GDF subfamily in a wide range of tumors, highlights the important role of GDF15 in HCC ecosystem, and provides important biomarkers and potential therapeutic targets for future research.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"92"},"PeriodicalIF":6.1,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512655","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":"Correction: Single-nucleus RNA sequencing reveals distinct pathophysiological trophoblast signatures in spontaneous preterm birth subtypes.","authors":"Cherilyn Uhm, Jianlei Gu, Weina Ju, Stephanie Pizzella, Hande Oktay, Joyce Yao-Chun Peng, Sararose Guariglia, Yong Liu, Hongyu Zhao, Yong Wang, Ramkumar Menon, Nanbert Zhong","doi":"10.1186/s13578-025-01421-x","DOIUrl":"10.1186/s13578-025-01421-x","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"90"},"PeriodicalIF":6.1,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508989","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":"The human testis-specific protein Y-linked (TSPY) is a male-specific cancer-testis antigen capable of eliciting significant immune responses and elimination of positive tumor cells in hepatocellular carcinoma.","authors":"Tatsuo Kido, Yun-Fai Chris Lau","doi":"10.1186/s13578-025-01432-8","DOIUrl":"10.1186/s13578-025-01432-8","url":null,"abstract":"<p><p>The testis-specific protein Y-linked (TSPY) is a male-specific cancer-testis antigen specifically expressed in germ cells of the testis under normal conditions and various cancers, particularly in hepatocellular carcinoma (HCC), under oncogenic conditions. It binds to cyclin B and exacerbates the cyclin B-CDK1 phosphorylation of factors important for mitotic/meiotic divisions. To determine if such TSPY proliferative actions could contribute to various male-biases in liver cancer, TSPY transgene was expressed in an oncogene-induced preclinical mouse model of HCC, using the hydrodynamic tail vein injection strategy. The results showed that TSPY expression suppressed tumor cell growth at early stage but could evolve to resume oncogenic progression at late stage in this mouse model. Transcriptome and bioinformatic analyses demonstrated that significant immune and inflammatory responses were activated in early stage of the cancer, resulting in elimination of positive tumor cells. Significant TSPY antibodies were present in the sera of positive mice, similar to the presence of autoantibodies in the sera of patients positive for TSPY in their tumors. Flow cytometry and cellular protein fractionation analyses of positive tumor cells showed that TSPY protein could be mislocalized on the cell surface and likely be responsible for the humoral immunity. Additional studies demonstrated that TSPY peptides were produced and could form complexes with MHC-I molecules and be presented on the cell surface, thereby eliciting robust cytotoxic T cell responses and killing of positive tumor cells. Importantly these immune responses diminished and TSPY could exacerbate oncogenic growth at late stage. These findings suggest that as a male-specific cancer-testis antigen, TSPY is extremely immunogenic capable of eliciting robust immune and inflammatory responses at the early stage and is a significant candidate for development of immunotherapeutics, such as therapeutic cancer vaccine and antibody-drug conjugates, in treatments of hepatocellular carcinoma in men.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"88"},"PeriodicalIF":6.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498949","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":"Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice.","authors":"Guang Yang, Yang Zhao, Chenyi Zhao, Jinglan Yan, Yucen Xia, Kun Li, Yongkang Wu, Xingyu Wang, Meng Zhang, Yongjun Chen, Ying Xu","doi":"10.1186/s13578-025-01422-w","DOIUrl":"10.1186/s13578-025-01422-w","url":null,"abstract":"<p><p>Anxiety occurs in the early stage of cognitive disorders, which can exacerbate cognitive impairment. However, the pathogenesis of this kind of anxiety remains unclear. In this study, we investigated anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout (PS cDKO) mice, a model of progressive cognitive impairment, using behavioral tests and electrophysiological recordings. Disrupted excitatory/inhibitory (E/I) balance was observed in pyramidal neurons (PNs) of the ventral hippocampus (vHPC) CA1 (vCA1) region of PS cDKO mice. Meanwhile, PV + interneurons showed hypoexcitability, associated with increased outward K⁺ currents due to elevated Kv1.1 potassium channel levels. Importantly, genetic or pharmacological inhibition of Kv1.1 restored PV + interneuron activity and reduced anxiety-like behaviors. These findings highlight a role of Kv1.1 in controlling PV + interneuron excitability, suggesting that targeting Kv1.1 in vCA1 PV + interneurons could mitigate anxiety in early-stage cognitive dysfunction.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"89"},"PeriodicalIF":6.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12199491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498948","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":"FRRS1L variants and ferriheme overload drive hyperpigmentation and systemic Iron overload in lanping black bone sheep.","authors":"Deping Han, Yuanyuan Zhang, Weidong Deng, Xue Yang, Jianfei Chen, Guoying Hua, Hesham Y A Darwish, Huaming Mao, Xiao Gou, Jiankui Wang, Kai Cui, Yuhao Ma, Yurong Tai, Xianggui Dong, Yanzhu Yao, Zu Yang, Suying Cao, Zhengquan Yu, Wansheng Liu, Xuemei Deng","doi":"10.1186/s13578-025-01426-6","DOIUrl":"10.1186/s13578-025-01426-6","url":null,"abstract":"","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"87"},"PeriodicalIF":6.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144486771","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}