Cellular & Molecular Biology Letters最新文献

{"title":"RSL3 promotes PARP1 apoptotic functions by distinct mechanisms during ferroptosis.","authors":"Dejian Chen, Fei Xie, Yimei Mo, Dan Qin, Binjiao Zheng, Lingyan Chen","doi":"10.1186/s11658-025-00785-9","DOIUrl":"10.1186/s11658-025-00785-9","url":null,"abstract":"<p><strong>Background: </strong>The classical ferroptosis activator RSL3 targets enzymes with nucleophilic active sites, primarily acting on glutathione peroxidase 4 (GPX4) to trigger ferroptosis. Recent studies identify RSL3 as a potential pro-apoptotic agent. However, the mechanism by which RSL3 induces apoptosis during ferroptosis remains elusive. Poly(ADP-ribose) polymerase (PARP1) determines cell fate in response to DNA damage, where its loss or cleavage by activated caspase-3 induces apoptosis to attenuate tumor progression. We elucidate a novel mechanism underlying PARP1 regulation, encompassing both its caspase-dependent cleavage and full-length depletion during RSL3-mediated ferroptosis-apoptosis crosstalk.</p><p><strong>Methods: </strong>To investigate the role of RSL3 during ferroptosis, we treated several cancer cells of different histological types with varying doses of RSL3 to induce apoptosis. The regulatory proteins of PARP1 were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The N⁶-methyladenosine (m⁶A) modification level of PARP1 was determined by m⁶A RNA immunoprecipitation (MeRIP)-qPCR analysis. Additionally, an RNA immunoprecipitation (RIP)-qPCR assay was performed to identify the target protein of the m⁶A site of PARP1. Furthermore, we established a mouse xenograft model of PARP inhibitor (PARPi)-resistant cells to analyze the effect of RSL3 on PARPi-resistant tumor growth.</p><p><strong>Results: </strong>RSL3 triggers two parallel apoptotic pathways via increasing reactive oxygen species (ROS) production during ferroptosis: (1) caspase-dependent PARP1 cleavage and (2) DNA damage-dependent apoptosis resulting from reduced full-length PARP1. The latter occurs through inhibition of METTL3-mediated m⁶A modification and subsequent suppression of PARP1 translation. Moreover, we found that RSL3 retains pro-apoptotic functions in PARPi-resistant cells and effectively inhibits PARPi-resistant xenograft tumor growth in vivo.</p><p><strong>Conclusions: </strong>RSL3 orchestrates ferroptosis-apoptosis crosstalk via PARP1, demonstrating therapeutic potential against tumorigenesis, particularly in PARPi-resistant malignancies.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"109"},"PeriodicalIF":10.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211726","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}

{"title":"Hypoimmune stem cells and islets: hype or a true breakthrough in diabetes treatment?","authors":"Karim E Shalaby, Essam M Abdelalim","doi":"10.1186/s11658-025-00786-8","DOIUrl":"10.1186/s11658-025-00786-8","url":null,"abstract":"<p><p>Immune-resistant pancreatic islets hold great promise for advancing diabetes cell therapy. Two key approaches, hypoimmunogenic pluripotent stem cells (PSCs) and hypoimmunogenic cadaveric islets, aim to overcome immune rejection in islet transplantation. Human PSCs provide a versatile source of insulin-producing cells, but immune rejection remains a major barrier. Recent advances in gene-editing technologies have enabled the modification of PSCs and cadaveric islets to reduce their immunogenicity. These cells can be engineered to express human leukocyte antigen (HLA)-negative profiles, while overexpressing immunoregulatory factors such as CD47, PD-L1, and HLA-G to evade T cell and natural killer (NK) cell immune-mediated responses. These modifications aim to generate \"off-the-shelf\" islet cell therapies compatible with a wide range of patients, potentially eliminating the need for immunosuppressants. However, ensuring long-term safety and functionality remains a challenge. Potential risks such as immune escape, viral infections, and tumorigenicity must be carefully addressed through additional safety measures. This review explores different approaches for generating hypoimmunogenic islets, recent advances in overcoming immune rejection, and key hurdles that need to be addressed for widespread clinical use for patients with diabetes. It also compares the potential benefits and limitations of hypoimmunogenic cadaveric islets versus hPSC-derived islets, providing insights into their future clinical applications.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"112"},"PeriodicalIF":10.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212044","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}

{"title":"The emerging role of human transmembrane RGD-based counter-receptors of integrins in health and disease.","authors":"Carlos Cabañas, Elisa Rossi, Ruben A Bartolomé, Kai Doberstein, Peter Altevogt, J Ignacio Casal, Carmelo Bernabeu","doi":"10.1186/s11658-025-00787-7","DOIUrl":"10.1186/s11658-025-00787-7","url":null,"abstract":"<p><p>Most of the canonical Arg-Gly-Asp (RGD)-containing integrin ligands are extracellular matrix proteins, such as fibronectin, vitronectin and fibrinogen, which regulate cell-ECM adhesion processes. However, during the last years, several reports have demonstrated the existence of non-canonical RGD-containing integrin ligands that are cell surface transmembrane proteins. At variance with the canonical extracellular matrix integrin ligands, the RGD-containing cell surface integrin ligands are involved in cell-cell adhesion processes and function as \"integrin counter-receptors\". We propose in this review grouping these transmembrane proteins, which include endoglin, cadherin-5, cadherin-6, cadherin-17, ADAM15, and L1CAM, under the newly coined acronym RGD-ICRs (RGD-containing Integrin Counter-Receptors). We present and discuss the structure of RGD-ICRs, their RGD-based interactions with integrins, the specific signaling pathways triggered in different cell types, as well as their pathophysiological involvement. It can be postulated that RGD-ICRs constitute an emerging group of non-canonical RGD-based integrin counter-receptors. In spite of being encoded by different and independent genes and involved in different pathophysiological processes, all of them appear to have undergone a strong evolutionary convergence in order to acquire the same functional capacity to bind integrins via the RGD motif. Importantly, these RGD-ICRs are also emerging as novel biomarkers and therapeutic targets, with promising clinical potential in a wide array of pathologies.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"110"},"PeriodicalIF":10.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211681","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}

{"title":"Programmed cell death in triple-negative breast cancer.","authors":"Yaqi Liu, Jinwei He, Jialu Chen, Tianshun Chen, Wei Li, Zhihui Yang, Fancai Zeng","doi":"10.1186/s11658-025-00789-5","DOIUrl":"10.1186/s11658-025-00789-5","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a particularly aggressive and therapeutically challenging subtype of breast cancer, defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. This absence of actionable molecular targets contributes to its resistance to conventional treatments. This review provides an overview of the mechanistic functions, interrelated processes, and therapeutic implications of several programmed cell death (PCD) pathways-including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis-in the context of TNBC pathogenesis and treatment. A conceptual framework is proposed for leveraging these interconnected cell death pathways as a basis for novel targeted interventions. Given the complex interplay among various PCD forms characterized by shared features such as inflammation, mitochondrial dysfunction, and overlapping molecular mediators, this integrated network offers promising opportunities for combinatorial therapeutic strategies. Modulation of one cell death pathway may influence others, potentially amplifying therapeutic efficacy. Furthermore, these PCD pathways are highly relevant to immunotherapy outcomes, offering a foundation for synergistic treatment modalities. This review provides an in-depth analysis of the crosstalk between immune-based therapies and PCD, along with a comprehensive discussion of derived therapeutic approaches. However, tumor diversity, resistance mechanisms, and discrepancies between preclinical models and human physiology pose major challenges in applying these findings clinically. The overarching goal is to present innovative insights and strategies to enhance the clinical management of TNBC and ultimately improve patient outcomes.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"111"},"PeriodicalIF":10.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12492730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211575","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}

{"title":"Crosstalk between endothelial cells and osteoblasts stimulates ALP via Notch signaling and RANKL/OPG ratio independently of Notch signaling in vitro.","authors":"Katharina Wirsig, Nina Bürger, Anne Bernhardt","doi":"10.1186/s11658-025-00793-9","DOIUrl":"10.1186/s11658-025-00793-9","url":null,"abstract":"<p><strong>Background: </strong>Bone remodeling requires a complex interplay between osteogenesis and angiogenesis, orchestrated by yet not fully understood intricate signaling pathways in osteoblasts and endothelial cells.</p><p><strong>Methods: </strong>In the present study, co-cultures of primary human osteoblasts and human umbilical vein endothelial cells (HUVEC) were compared with osteoblast cultures treated with dexamethasone (Dex), vascular endothelial growth factor (VEGF), their combination, or VEGF in the presence of Notch inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT). Cellular behavior was analyzed at morphological, gene expression, and protein levels to identify key regulators in the interplay between osteoblasts and endothelial cells.</p><p><strong>Results: </strong>Dex and VEGF additively increased alkaline phosphatase (ALP) in osteoblast-HUVEC co-cultures, but not in osteoblast cultures. Furthermore, Dex reduced the receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio in osteoblasts. This effect was reversed in the presence of VEGF, but only in co-culture, indicating a direct action of endothelial cells, rather than VEGF itself, in stimulating RANKL and reducing OPG in osteoblasts. In addition, Notch signaling, specifically NOTCH1 and DLL4, was induced in response to VEGF solely in co-cultures. The presence of Notch inhibitor DAPT suppressed VEGF-induced stimulation of ALP but not RANKL/OPG ratio.</p><p><strong>Conclusions: </strong>Our findings provide novel evidence for the significant role of endothelial cells in bone remodeling, specifically in regulating ALP expression and activity of osteoblasts via the Notch signaling pathway and RANKL/OPG ratio independent of Notch. This study underscores the applicability and significance of multicellular tissue models for studying bone turnover processes in vitro, thereby reducing the reliance on animal testing.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"108"},"PeriodicalIF":10.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12490079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212050","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}

{"title":"FET fusion oncoproteins enrich SWI/SNF complex subtypes and interaction partners.","authors":"Malin Lindén, Lisa Andersson, Heba Albatrok, Vilma Canfjorden, Emma Jonasson, Kajsa Grönqvist, Daniel Sjövall, Pekka Jaako, Rossella Crescitelli, Henrik Fagman, Pierre Åman, Anders Ståhlberg","doi":"10.1186/s11658-025-00792-w","DOIUrl":"10.1186/s11658-025-00792-w","url":null,"abstract":"<p><strong>Background: </strong>FET (FUS, EWSR1, and TAF15) fusion oncoproteins are characteristic for several sarcomas and leukemias, including myxoid liposarcoma and Ewing sarcoma. FET oncoproteins interact with the SWI/SNF chromatin remodeling complex subtypes cBAF, PBAF, and GBAF, but their impact on SWI/SNF compositions, interactions, and downstream epigenetic effects remains elusive.</p><p><strong>Methods: </strong>We employ a comprehensive immunoprecipitation and quantitative mass spectrometry approach to determine the impact of FET oncoproteins on SWI/SNF composition and their interactomes. Validation of complex composition and interaction partners is performed by glycerol gradient sedimentation assays and co-immunofluorescence analysis. Furthermore, we determine the differential chromatin accessibility and gene regulation in FET sarcomas using assay for transposase-accessible chromatin sequencing and RNA sequencing, respectively.</p><p><strong>Results: </strong>Our data show that FET sarcomas have distinct SWI/SNF complex compositions, with different subunit paralogs and subtype-specific components that utilize distinct sets of interaction partners, including specific transcription factors. We show that FET oncoproteins cause no major disruption of the SWI/SNF complex composition. Instead, FUS::DDIT3-bound SWI/SNF complexes in myxoid liposarcoma cells are enriched in PBAF and GBAF components as well as most interaction partners.</p><p><strong>Conclusions: </strong>These data suggest that FET oncoproteins act together with fully assembled and functional SWI/SNF complexes and recruited interaction partners. Finally, our data reveal that the SWI/SNF compositions, interactomes, and epigenetic background contribute to the tumor type in FET sarcoma. Trial registration Clinical trial number: not applicable.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"107"},"PeriodicalIF":10.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130091","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}

{"title":"Atypical cadherin FAT1 promotes tumorigenesis by suppressing autophagic cell death in glioblastoma under hypoxia or nutrient stress.","authors":"Yakhlesh Gupta, Sanjeev Goswami, Manvi Arora, Nargis Malik, Khushboo Irshad, Archismita Kundu, Srinivas H Gowda, Mani Kapoor, Shruti Gupta, Tapas Chandra Nag, Vaishali Suri, Ashish Suri, Parthaprasad Chattopadhyay, Subrata Sinha, Kunzang Chosdol","doi":"10.1186/s11658-025-00783-x","DOIUrl":"10.1186/s11658-025-00783-x","url":null,"abstract":"<p><strong>Background: </strong>Autophagy, a conserved intracellular degradation process, plays dual roles in cancer, promoting survival under stress or mediating cell death through deregulated autophagy. Atypical cadherin FAT1 functions as an oncogene or tumor suppressor in a context-dependent manner. Our previous work identifies the oncogenic role of FAT1 in glioblastoma. Deregulated autophagy has been documented in glioma. Here, we investigated the role of FAT1 in regulating autophagy and its implications for glioblastoma growth and progression.</p><p><strong>Methods: </strong>CRISPR-Cas9 mediated FAT1 knockout was generated in glioblastoma (U87MG and LN229) and other cancers such as hepatocellular carcinoma (HepG2 and HUH7) and pancreatic adenocarcinoma (MIAPaca-2 and Panc-1) cells. The cell viability and growth under hypoxia ± serum deprivation were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Annexin V-FITC assays. Autophagy markers were assessed by quantitative polymerase chain reaction (qPCR), Western blot, immunocytochemistry (ICC), and immunohistochemistry (IHC). Autophagosomes were visualized by transmission electron microscopy (TEM), and puncta formation was analyzed by transfecting the cells with pEGFP-LC3. Autophagy flux was evaluated by analyzing p62/SQSTM1 levels, and the GFP/RFP ratio using pMRX-IP-GFP-LC3-RFP-LC3ΔG. In vivo, FAT1-knockout U87MG xenografts in nude mice were analyzed for tumor growth and autophagy marker expression. Surgically resected glioblastoma tumors from our hospital and The Cancer Genome Atlas (TCGA) dataset were analyzed for autophagy marker expression and patient survival correlations.</p><p><strong>Results: </strong>FAT1-knockout glioblastoma (U87MG and LN229) cells demonstrated reduced survival and colony numbers under normoxia and hypoxia with serum deprivation, facilitated by autophagy-dependent cell death. These cells exhibited upregulated autophagy markers, increased LC3 puncta, autophagosomes, and autophagy flux. FAT1-knockout glioblastoma cells showed decreased total and phospho-mTOR levels. FAT1-knockout xenografts showed reduced tumor progression with increased LC3II, Beclin1, and autophagosomes. Human glioblastoma tumors and TCGA glioblastoma data revealed an inverse expression correlation of FAT1 with LC3B/Beclin1, tumors with high-FAT1/low-LC3B expression were associated with poor patient survival. FAT1 also regulated autophagy in hepatocellular and pancreatic cancers.</p><p><strong>Conclusion: </strong>Our findings indicate that FAT1 mediates pro-tumorigenic function by suppressing autophagic cell death in glioblastoma and other cancers. FAT1 may serve as a potential therapeutic adjuvant along with standard therapeutic regimens for treating cancers with high FAT1 expression having an oncogenic role.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"106"},"PeriodicalIF":10.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991412","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}

{"title":"A novel SWI/SNF complex promotes triple-negative breast cancer progression.","authors":"Wen-Yi Sheng, Yue Zhu, Shi-Qi Liu, Qi-Yan Huang, Wei-Feng Qian, Jia-le Cheng, Huan-Huan Huang, Wen-Jie Wang, You Meng","doi":"10.1186/s11658-025-00788-6","DOIUrl":"10.1186/s11658-025-00788-6","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is the most prevalent and fatal cancer affecting women worldwide. The SWI/SNF complexes exhibit the ability to selectively replace subunits, thereby enabling a wide range of epigenetic functions. As an accessory subunit of this complex, ARID1B is critically involved in modulating chromatin accessibility and transcriptional regulation. Nevertheless, its precise contribution to TNBC pathogenesis remains poorly understood.</p><p><strong>Methods: </strong>ARID1B expression levels in TNBC were detected using immunofluorescence and real-time quantitative polymerase chain reaction (PCR). To investigate ARID1B's biological functions in TNBC, a series of in vitro assays were conducted, complemented by subcutaneous tumor xenograft models. Mass spectrometry analysis was employed to identify ARID1B-interacting proteins, while RNA-sequencing (RNA-seq) was performed to screen downstream target genes regulated by ARID1B. The transcriptional regulatory mechanism of ZNF382 mediated by ARID1B was further validated through dual-luciferase reporter assays and Chromatin immunoprecipitation (ChIP)-qPCR. To determine if ZNF382 knockdown could reverse the cellular effects of ARID1B, SMARCC2, and SMARCB1 inhibition, functional rescue experiments were conducted.</p><p><strong>Results: </strong>We identified ARID1B as a notable E3 ubiquitin ligase gene associated with breast cancer prognosis, particularly serving as a risk prognostic factor in TNBC. Contrary to its previously reported function as an E3 ubiquitin ligase, we observed that ARID1B transcriptionally represses ZNF382 by forming a novel SWI/SNF complex with SMARCC2 and SMARCB1. This newly assembled complex promotes TNBC proliferation and migration, highlighting a previously unrecognized mechanism of ARID1B in cancer development.</p><p><strong>Conclusions: </strong>This research enhances the understanding of the intricate roles played by SWI/SNF complex components in TNBC and bridges the gap between the structural specificity of SWI/SNF assembly and the progression of cancer. These findings could potentially unveil novel therapeutic targets for TNBC, thereby advancing the development of more efficacious treatment approaches for this highly aggressive malignancy.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"105"},"PeriodicalIF":10.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944188","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}

{"title":"CCHCR1 links P-body proteins to the centrosome and is required for ciliogenesis through interacting with OFD1 and PCM1.","authors":"Junshan Zhang, Qiwen Wu, Shanqiang Zhang, Stephen Cho Wing Sze, Chunman Li","doi":"10.1186/s11658-025-00780-0","DOIUrl":"https://doi.org/10.1186/s11658-025-00780-0","url":null,"abstract":"<p><strong>Background: </strong>Processing bodies (P-bodies) are nonmembranous ribonucleoprotein (RNP) granules located in the cytosol that function as assembly hubs for RNA storage and degradation. Although there are reports indicating that certain P-body proteins are also present at the centrosome and participate in primary cilia development, how these P-body proteins localize to the centrosome remains unclear. In mammalian cells, coiled-coil alpha-helical rod protein 1 (CCHCR1) is localized to both the P-bodies and centrosomes, where it interacts with the P-body component enhancer of mRNA-decapping protein 4 (EDC4) as well as a range of centriolar satellite components, yet its cellular function remains poorly characterized.</p><p><strong>Methods: </strong>Biotin identification (BioID) coupled with mass spectrometry, immunoprecipitation (IP), glutathione S-transferase (GST) pull-down, and acceptor bleaching fluorescence resonance energy transfer (AB-FRET) assay were used to explore and identify protein-protein interactions. Gene overexpression, RNA interference-based gene knockdown, CRISPR-Cas9-mediated gene knockout, and immunofluorescence (IF) were applied to elucidate the underlying molecular mechanism.</p><p><strong>Results: </strong>We identified that CCHCR1 interacts with oral-facial-digital syndrome 1 protein (OFD1) via its C-terminal coiled-coil domain. The centrosomal localization of CCHCR1 is determined by OFD1 and pericentriolar materials 1 (PCM1). We also found that CCHCR1 recruits P-body proteins to the centrosome through interacting with EDC4 via its N-terminal coiled-coil domain. Depletion of either CCHCR1 or P-body components EDC4 and DEAD-Box Helicase 6 (DDX6) impairs ciliogenesis.</p><p><strong>Conclusions: </strong>CCHCR1 acts as a linker that recruits P-body proteins to the centrosome and is essential for cilia development. The recruitment of P-body proteins to the centrosome via CCHCR1 is also one of the mechanisms by which PCM1 and OFD1 are involved in ciliogenesis.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"103"},"PeriodicalIF":10.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944260","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}

{"title":"Radiation-sensitive circRNA promotes intestinal regeneration.","authors":"Hui Cai, Xin Liang, Shazhen Ai, Hao Sun, Xinyu Zhang, Qianying Lu, Qingshan Yang, Ying Li, Di Zhao, Manman Zhang, Kaihua Ji, Yan Wang, Qiang Liu","doi":"10.1186/s11658-025-00782-y","DOIUrl":"https://doi.org/10.1186/s11658-025-00782-y","url":null,"abstract":"<p><strong>Background: </strong>The intestine is one of the most sensitive organs to ionizing radiation (IR), and radiation-induced intestinal injury (RIII) impacts the quality of life of patients undergoing radiotherapy. There are limited early diagnostic biomarkers and specific medicines clinically approved for RIII. Therefore, we sought to identify new theranostic targets to prevent RIII and to facilitate the reestablishment of the intestinal epithelium. Circular RNAs (circRNAs) are widely appreciated as pervasive regulators of many diseases and multiple biological processes, while whether and how specific circRNAs are involved in radiation-induced intestinal injury remains largely unknown.</p><p><strong>Methods: </strong>Differentially expressed circRNAs were analyzed and verified via RNA sequencing. The function of an intestine-specific circRNA (termed circDmbt1(3,4,5,6)) on cell proliferation, apoptosis, and DNA damage level after radiation was explored in vitro, and the underlying mechanism was further investigated. Ultimately, intestinal organoids and mice model were used to verify the role of circDmbt1(3,4,5,6) on radiation-induced intestinal injury.</p><p><strong>Results: </strong>Primarily expressed in intestinal stem cells, CircDmbt1(3,4,5,6) was downregulated in mice intestines after 14 Gy abdominal radiation and showed timely relationship with intestinal injury level. CircDmbt1(3,4,5,6) promoted the proliferation and alleviated cell apoptosis and DNA damage level of intestinal epithelial cells and promoted organoids survival after radiation compared with control groups. In vivo experiments showed that compared with control groups, overexpression of circDmbt1(3,4,5,6) could increase intestinal length; enhance epithelial integrity and the percentage of proliferative cells, stem cells, paneth cells, and goblet cells; and promote intestinal adaption after radiation. Mechanistically, circDmbt1(3,4,5,6) protects intestines from IR via circDmbt1(3,4,5,6)/miR-125a-5p/STAT3.</p><p><strong>Conclusions: </strong>CircDmbt1(3,4,5,6), a novel promising RIII bio-marker, responses rapidly at the early stage after 14 Gy abdominal irradiation, and exogenous expression of circDmbt1(3,4,5,6) could promote intestinal fitness in RIII. We reveal that the circDmbt1(3,4,5,6)/miR-125a-5p/STAT3 axis is important to the regeneration of the intestinal epithelium after radiation-induced damage, providing a potential diagnostic and therapeutic target for RIII.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":"30 1","pages":"104"},"PeriodicalIF":10.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944351","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}