Cell Cycle最新文献

{"title":"The methyltransferase METTL3 promotes the progression of breast cancer cells via regulating EGF m6A modification.","authors":"Jiaqing Liu, Han Fang, Xinhao Yang, Yi Lu, Enjie Li, Meina Wang, Zhigang Hu","doi":"10.1080/15384101.2025.2570258","DOIUrl":"https://doi.org/10.1080/15384101.2025.2570258","url":null,"abstract":"<p><p>Ranking second out of new cancer cases, breast cancer (BRCA) is the leading cause of cancerous death among women globally. Methyltransferase-like 3 (METTL3), as the well-known N6‑methyladenosine (m6A) \"writer\" with catalytic function, regulates cancer progression through specific downstream targets, but its interplay with epidermal growth factor (EGF) signaling in BRCA is poorly defined. Here, we depict a METTL3-m6A-EGF axis in BRCA, where BRCA cell properties were affected by METTL3 through m6A-dependent expression of EGF. We observed the correlation between METTL3 expression in BRCA tissues and negative prognosis through bioinformatics analysis and RT-qPCR. <i>In vitro</i> lentiviral-mediated METTL3 knockdown suppressed proliferation and migration, while the <i>in vivo</i> tumor formation experiment in nude mice validated the tumor-promoting effect of METTL3. Hematoxylin-eosin staining and immunohistochemistry also showed the tumor-promoting effect of METTL3. Mechanistically, METTL3 stabilized EGF mRNA via m6A modification, as evidenced by MeRIP-qPCR and Western blotting. Notably, METTL3 maintains EGF/EGFR signaling, and its overexpression leads to insensitivity to gefitinib and adriamycin. We naturally conclude that METTL3 is a central epigenetic regulator of EGF-driven BRCA progression, providing a rationale for targeting METTL3 to overcome chemotherapeutic resistance.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-14"},"PeriodicalIF":3.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of progression markers for prostate cancer.","authors":"Jie Song, Yang Zhou, Harald Hedman, Tommi Rantapero, Maréne Landström","doi":"10.1080/15384101.2025.2563930","DOIUrl":"https://doi.org/10.1080/15384101.2025.2563930","url":null,"abstract":"<p><p>TGFβ functions as a tumor suppressor or promoter, depending on the context, making TGFβ a useful predictive biomarker. Genes related to TGFβ signaling and Aurora kinase were tested for their ability to predict the progression risk of primary prostate tumors. Using data from The Cancer Genome Atlas (TCGA), we trained an elastic-net regularized Cox regression model including a minimal set of gene expression, copy number (CN), and clinical data. A multi-step feature selection and regularization scheme was applied to minimize the number of features while maintaining predictive power. An independent hold-out cohort was used to validate the model. Expanding from prostate cancer, predictive models were similarly trained on all other eligible cancer types in TCGA. <i>AURKA</i>, <i>AURKB</i>, and <i>KIF23</i> were predictive biomarkers of prostate cancer progression, and upregulation of these genes was associated with promotion of cell-cycle progression. Extending the analysis to other TCGA cancer types revealed a trend of increased predictive performance on validation data when clinical features were complemented with molecular features, with notable variation between cancer types and clinical endpoints. Our findings suggest that TGFβ signaling genes, prostate cancer related genes and Aurora kinases are strong candidates for patient-specific clinical predictions and could help guide personalized therapeutic decisions.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-18"},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction.","authors":"","doi":"10.1080/15384101.2025.2534742","DOIUrl":"https://doi.org/10.1080/15384101.2025.2534742","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-2"},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> modulation of adipocyte differentiation by tenofovir alafenamide/disoproxil fumarate following challenge with recent ARV drugs.","authors":"Maria Aurora Carleo, Emiliano Del Genio, Aldo Mileo, Alessandra Guida, Raffaele Pastore, Angela Lucariello, Mariarosaria Boccellino, Alfonso Baldi, Paolo Maggi, Vincenzo Esposito, Antonio De Luca","doi":"10.1080/15384101.2025.2563396","DOIUrl":"https://doi.org/10.1080/15384101.2025.2563396","url":null,"abstract":"<p><p>Previous studies demonstrated that integrase-strand-transfer-inhibitors (INSTIs) promote adipocyte differentiation, while nucleoside-reverse-transcriptase-inhibitors (NRTIs) tenofovir-alafenamide-fumarate (TAF) and tenofovir-disoproxil-fumarate (TDF), inhibit adipogenesis. NRTIs were shown to counteract the pro-adipogenic effects of INSTIs[6]. However, the effects of non-nucleoside-reverse-transcriptase-inhibitors (NNRTIs) and of the novel long-acting INSTI cabotegravir (CAB), on adipogenesis, alone or in combination with NRTIs or other INSTIs, remain unclear. This study aims to elucidate the impact of NNRTIs and recent INSTIs on adipogenesis. 3T3-L1 cells were used as an adipogenesis in vitro model. The NNRTIs doravirine (DOR) and rilpivirine (RPV) were tested alone and in combination with DTG, CAB, TDF, TAF. Adipogenesis was assessed by Oil-Red-O-staining and by measuring expression-levels of peroxisome-proliferator-activated-receptor-gamma (PPARγ) and CCAAT/enhancer-binding-protein-alpha (C/EBPα). Moreover, Fibroblast-marker ER-TR7 was assessed by immunohistochemistry. CAB, DOR, and RPV promoted adipogenesis, with CAB and DOR showing greater effects. In combination, NNRTIs enhanced the adipogenic effects of CAB and DTG. Conversely, TAF and TDF, when paired with RPV or DOR, inhibited adipogenesis. NNRTIs and CAB increased ER-TR7 expression, suggesting fibroblastic differentiation. Finally, NNRTIs and INSTIs promote adipogenesis and induce fibroblastic features in 3T3-L1 cells. Contrarily, TAF and TDF exhibited an antagonistic effect on adipogenesis when combined with certain antiretrovirals, supporting our previous research.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-10"},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rewiring the mTOR, CDH1, APC/C, PFKFB3 axis: a glycolytic pulse to ignite the G0/G1 gateway.","authors":"Gaetano Santulli","doi":"10.1080/15384101.2025.2567160","DOIUrl":"https://doi.org/10.1080/15384101.2025.2567160","url":null,"abstract":"","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-3"},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte-derived stanniocalcin-1 orchestrates epileptogenesis through NF-κB-dependent neuroinflammation.","authors":"Xinyue Guan, Wenzeng Wang, Qiannan Song, Kexin Li, Hong Chen","doi":"10.1080/15384101.2025.2566293","DOIUrl":"https://doi.org/10.1080/15384101.2025.2566293","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the expression pattern of astrocyte-derived STC1 in TLE and elucidate the molecular mechanisms by which STC1 regulates neuroinflammation and seizures through the NF-κB signaling pathway.</p><p><strong>Methods: </strong>A TLE model was established by intrahippocampal injection of kainic acid (KA) in mice. STC1 expression levels and cellular localization in the hippocampus of TLE mice were examined. Adeno-associated virus-mediated gene overexpression and shRNA knockdown approaches were employed to investigate the effects of STC1 on neuroinflammatory responses, neuronal survival, and seizure activity. qRT-PCR and immunofluorescence methods were further utilized to evaluate inflammatory cytokine levels and NF-κB signaling pathway activity.</p><p><strong>Results: </strong>STC1 expression was upregulated in hippocampal tissues of TLE mice, with double immunofluorescence showing STC1 predominantly localized in GFAP-positive reactive astrocytes. STC1 overexpression significantly exacerbated KA-induced neuroinflammation, along with enhanced microglial activation. STC1 knockdown attenuated neuroinflammatory responses. Nissl staining and NeuN immunohistochemistry confirmed that STC1 aggravated KA-induced neuronal loss. STC1 overexpression promoted p65 phosphorylation and nuclear translocation, activating the NF-κB signaling pathway.</p><p><strong>Conclusion: </strong>This study reveals the molecular mechanism by which astrocyte-derived STC1 promotes TLE-associated neuroinflammation and neuronal injury through activation of the NF-κB signaling pathway, elucidating the crucial role of the astrocyte-STC1-NF-κB axis in epileptogenesis.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-19"},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The GABBR1/miR-19b-3p/WNT2B axis regulates insulin resistance and liver injury in diabetes with viral infection: mechanistic and therapeutic insights.","authors":"Rui Yang, Jiangling Zhu, Lin Zou, Yingxuan Li, Li Peng, Xing Wang, Qian Xi, Fei Sun, Junhua Ma, Xia Chen","doi":"10.1080/15384101.2025.2564744","DOIUrl":"https://doi.org/10.1080/15384101.2025.2564744","url":null,"abstract":"<p><p>Insulin resistance (IR) is the main feature of type 2 diabetes mellitus. Furthermore, viral infection can aggravate the abnormal glucose metabolism in diabetic patients. GABBR1 can maintain normal glucose homeostasis, but its specific role in diabetes is not clear. We investigated the function of the GABBR1/miR-19b-3p/WNT2B axis <i>in vitro</i> and <i>in vivo</i>. miR-19b-3p and GABBR1 were overexpressed or knocked down in AML12 cells. Subsequently, these cells were treated with palmitic acid (PA) to induce damage or poly I : C to mimic viral infection. The degree of AML12 cell damage was assessed using the CCK-8 assay; inflammation levels were measured using ELISA; and IR indexes were determined using the Immunofluorescence kit and Western blot assay. The diabetic mice model was established to evaluate liver injury and IR. PA and poly I : C can reduce the activity of AML12 cells, increase apoptosis and inflammatory factor contents, weaken the ability of glucose uptake and consumption, enhance the production capacity, and reduce the level of GLUT4. GABBR1 mediates the targeted regulation of WNT2B by miR-19b-3p. PA and poly I : C also increased ALT, AST, inflammatory factors and miR-19b-3p levels, and decreased GABBR1 and WNT2B expression of mice. Liver cells showed swelling and many spherical lipid droplets. After miR-19b-3p knockdown and GABBR1 overexpression, the degree of liver injury and IR in AML12 cells and mice were alleviated. GABBR1 regulates miR-19b-3p/WNT2B axis to reduce liver injury, IR and inflammatory response, and improve the comorbidity of diabetes and viral infection. This pathway represents a potential therapeutic target for mitigating the comorbidity of diabetes and viral infection.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-20"},"PeriodicalIF":3.4,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on cell cycle arrest in dermal fibroblasts.","authors":"Meizhen Wu, Juanlie Luo, Wenling Yang, Zhiying Wei, Yaohua Li, Xiaojiao Pan","doi":"10.1080/15384101.2025.2557240","DOIUrl":"https://doi.org/10.1080/15384101.2025.2557240","url":null,"abstract":"<p><p>Cell cycle arrest in dermal fibroblasts is a critical biological process essential for maintaining skin homeostasis and serves as a central mechanism driving various skin pathologies. This review systematically summarizes the endogenous and exogenous factors triggering cell cycle arrest in dermal fibroblasts and their underlying molecular mechanisms, with a particular focus on the roles of key signaling pathways such as p53, TGF-β/Smad, and Wnt/β-catenin. Additionally, the dual effects of cell cycle arrest on the skin are discussed: transient arrest facilitates DNA damage repair and tissue regeneration, whereas prolonged arrest leads to cellular senescence, chronic inflammation, collagen degradation, and fibrosis. Advances in chemical compounds modulating cell cycle arrest are also highlighted, including potential therapeutic strategies for promoting or relieving cell cycle arrest. This review provides new insights into skin regenerative medicine and anti-aging therapies while identifying critical scientific questions for future research.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-18"},"PeriodicalIF":3.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and validation of predictive model based on endoplasmic reticulum stress-related genes for triple-negative breast cancer.","authors":"Yongqian Zhang, Hongmin Wang, Lingling Zhu, Xiaojing Chen, Min Zhao, Ming Liu","doi":"10.1080/15384101.2025.2557239","DOIUrl":"https://doi.org/10.1080/15384101.2025.2557239","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) poses challenges in treatment due to its inherent biological characteristics. Endoplasmic reticulum stress (ERS) has been associated with the development of TNBC. Hence, identifying ERS-related prognostic biomarkers is crucial for the early diagnosis and treatment of TNBC. In this study, we retrieved gene expression profiles from TNBC patients using The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) between TNBC tumor and normal tissues were identified using limma package. Using differential expression analysis, we identified 46 ERS-related DEGs. Through univariate Cox, LASSO, and multivariate COX regression analyses, we constructed a prognostic model consisting of 8 genes (IGFBP1, CFTR, THBS4, CREBRF, CLU, HDGF, DERL3, NCCRP1). This model demonstrated robust prognostic accuracy in TNBC patients, validated by the METABRIC dataset. Among the 8 prognostic genes, NCCRP1 showed the highest expression increase in BT-20 and MDA-MB-468 cells. Functional assays further revealed that NCCRP1 significantly promoted proliferation, migration, and invasion, while suppressing apoptosis and ERS in these TNBC cell lines. Our study highlights a strong association between ERS-related genes and the prognosis of TNBC patients. Moreover, we demonstrated that NCCRP1 exerts oncogenic effects in TNBC cells. It provides new insights and possible treatment targets for TNBC.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"1-22"},"PeriodicalIF":3.4,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular crossroads: identifying MAPK proteins bridging SMAD and dopamine pathways in breast cancer.","authors":"Przemysław Borawski, Tomasz Sirek, Agata Sirek, Nikola Zmarzły, Robert Nowakowski, Piotr Ossowski, Michał Chalcarz, Kacper Boron, Dariusz Boron, Krzysztof Bereza, Konrad Dziobek, Nina Skalska-Dziobek, Piotr Wyrobiec, Beniamin Oskar Grabarek","doi":"10.1080/15384101.2025.2549097","DOIUrl":"10.1080/15384101.2025.2549097","url":null,"abstract":"<p><p>The transforming growth factor-beta (TGF-β)/SMAD signaling pathway, mitogen-activated protein kinase (MAPK) signaling cascade, and dopamine receptor activity are all implicated in tumor progression. This study investigates molecular interactions among these pathways, identifying MAPK proteins that bridge SMAD and dopamine signaling in the context of breast cancer pathogenesis. A cohort of 405 breast cancer patients was categorized into molecular subtypes: luminal A (<i>n</i> = 130), luminal B HER2-negative (<i>n</i> = 100), luminal B HER2-positive (<i>n</i> = 96), non-luminal HER2-positive (<i>n</i> = 36), and triple-negative breast cancer (TNBC; <i>n</i> = 43). Transcriptomic profiling using microarrays and bioinformatics-based network analysis revealed differentially expressed genes across subtypes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate 11 key transcripts, and protein expression was quantified by enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) regulatory interactions were analyzed to assess post-transcriptional modulation. Among 167 differentially expressed genes, 14 were consistently altered across all subtypes. These included cell division cycle 42 (<i>CDC42</i>), KRAS proto-oncogene, GTPase (<i>KRAS</i>), and transforming growth factor beta 1 (<i>TGFB1</i>), which were upregulated, as well as fibroblast growth factor 2 (<i>FGF2</i>), fibroblast growth factor 7 (<i>FGF7</i>), and insulin-like growth factor 1 <i>(IGF1</i>), which were downregulated. miRNA analysis revealed miR-221, miR-222, and miR-16-5p as regulators of these pathways. ELISA confirmed reduced KIT, IGF1, and FGF family proteins in tumor tissues, with KRAS significantly upregulated. Protein interaction analysis highlighted key hubs linking MAPK, SMAD, and dopamine signaling. This study elucidates crucial molecular intersections between MAPK, SMAD, and dopamine pathways, identifying potential biomarkers and therapeutic targets for breast cancer.</p>","PeriodicalId":9686,"journal":{"name":"Cell Cycle","volume":" ","pages":"296-315"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}