Molecular and Cellular Biochemistry最新文献

{"title":"GPR55 senses lactate to sustain motility in prostate cancer cells.","authors":"Giovanna Sgrignani, Marta Iozzo, Lara Di Leonardo, Elisa Pardella, Erica Pranzini, Giulia Gangarossa, Giuseppina Comito, Luigi Ippolito, Elisa Giannoni, Paola Chiarugi","doi":"10.1007/s11010-025-05312-0","DOIUrl":"https://doi.org/10.1007/s11010-025-05312-0","url":null,"abstract":"<p><p>The enrichment of specific metabolites within the tumor microenvironment is emerging as a driver of tumor progression. Specifically, in prostate cancer (PCa), increased abundance of lactate is associated with primary-to-metastasis tumor spreading by supporting cancer cell invasiveness. Here, we highlight that the endocannabinoid receptor GPR55 is able to sense lactate and consequently trigger PCa cell amoeboid-like invasiveness, through the activation of the pro-migratory RhoA/MLC2 signaling pathway. These findings uncover a new role for GPR55 in sustaining lactate-driven PCa cell motility.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144160437","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":"Radial artery intima-media thickening is a sensitive marker of atherosclerosis and coronary artery stenosis, a lesson from a 6-year study of a spontaneous monkey model.","authors":"Jue Wang, Wen Zheng, Haibao Shang, Lin Pan, Ye Yuan, Wenli Chen, Chunguang Guo, Shihan Li, Xueting Sun, Jing Guo, Xiuqin Zhang","doi":"10.1007/s11010-025-05315-x","DOIUrl":"https://doi.org/10.1007/s11010-025-05315-x","url":null,"abstract":"<p><p>Atherosclerosis is the primary driver of cardiovascular and cerebral vascular diseases globally. Atherosclerotic plaques have been detected in multiple arterial locations, such as the aorta, carotids, and coronaries. However, it remains uncertain if there are variations in susceptibility and association among arteries of different calibers. Utilizing a spontaneous rhesus monkey model of metabolic syndrome (MetS), we assessed the susceptibility of atherosclerosis among the radial artery, femoral artery, and carotid artery and their correlation with coronary heart disease (CHD). The development of atherosclerosis in the three arteries mentioned above was evaluated by Intima-media thickness (IMT) and plaques using echo imaging over 6 years in a cohort of elderly monkeys with metabolic disorders. Coronary artery stenosis was assessed by coronary flow reserve (CFR) simultaneously. The diagnosis was further confirmed by histopathological examination, and RNA sequencing was employed to probe the transcriptional underpinnings of atherosclerotic development. The spontaneous development of atherosclerosis was observed in elderly monkeys, and the incidence of atherosclerosis was increased by three times in the MetS monkeys compared to the age-matched control group. During the 6-year follow-up, there was a notable increase in the IMT across all three arteries, with the radial artery showing the most pronounced thickening. Moreover, only the radial IMT correlated with CFR, suggesting its potential as a non-invasive diagnostic indicator for CHD. Histopathology confirmed the findings by echo imaging and identified different extracellular matrix (ECM) remodeling patterns in the arteries. In addition, transcriptomic analysis revealed that ECM remodeling and inflammation-related pathways were significantly upregulated in radial atherosclerotic samples, multiple inflammatory pathways were upregulated in the femoral lesion samples, and the carotid samples failed to enrich any pathways due to a lack of differentially expressed genes compared to the control samples. Non-human primates, which share extensive genetic and physiological similarities with humans, develop atherosclerosis spontaneously. This provides an invaluable platform for investigating the intricate mechanisms of arterial disease and evaluating potential treatments. Using the monkey model, we identified the radial artery as a sensitive indicator for assessing the occurrence and progression of atherosclerosis and coronary stenosis.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136112","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":"CD44 and SLC1A2 are commonly regulated but do not form a fusion transcript in ER+ breast cancer.","authors":"Francesca Bonechi, Marina Bacci, Nicla Lorito, Alfredo Smiriglia, Edoardo Pagliantini, Matteo Benelli, Icro Meattini, Andrea Morandi","doi":"10.1007/s11010-025-05308-w","DOIUrl":"https://doi.org/10.1007/s11010-025-05308-w","url":null,"abstract":"<p><p>Endocrine therapy (ET) is essential for managing ER+ HER2- breast cancer; however, resistance remains a significant clinical challenge. This study investigated whether CD44-SLC1A2 gene fusions, reported in gastrointestinal malignancies, contribute to ET resistance mechanisms in breast cancer. Although no CD44-SLC1A2 fusions were detected, high expression of CD44 and SLC1A2 was associated with poor survival outcomes and identified a therapy-resistant subpopulation sustained by aspartate and glutamate metabolism, highlighting potential metabolic vulnerabilities for future therapeutic intervention.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132637","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":"MAPK signaling mediates tamoxifen resistance in estrogen receptor-positive breast cancer.","authors":"Sepide Javankiani, Soheil Bolandi, Anvar Soleimani, Mohammad Saeed Soleimani Meigoli, Mahdis Parsafar, Sadaf Safaei, Mojgan Esmailpour, Sogol Nadimi, Nahal Aghajamal Avval, Seyed Mohammad Ali Fazayel, Zahra Zahed, Malihe Sharafi","doi":"10.1007/s11010-025-05304-0","DOIUrl":"10.1007/s11010-025-05304-0","url":null,"abstract":"<p><p>Tamoxifen is a cornerstone in the treatment of estrogen receptor (ER)-positive breast cancer, yet resistance to this therapy remains a significant clinical challenge. In most cases, the resistance phenotype is not caused by loss or mutation of the ER, but by changes in multiple proliferative and survival pathways. The mitogen-activated protein kinase (MAPK) signaling pathways regulate various cellular processes such as cell growth, proliferation, and apoptosis. This review provides a comprehensive analysis of molecular mechanisms that sustain MAPK activation and promote tamoxifen resistance. We evaluated molecular factors that promote the survival of tamoxifen-resistant cells through the regulation of MAPK signaling, including growth factors, RNA-binding proteins, non-genomic ER variants, and microRNAs. Mitochondrial dynamics and their regulation by MAPK highlight novel adaptive mechanisms employed by resistant cells to survive. Furthermore, MAPK-mediated phosphorylation of ERα enhances resistance through ligand-independent activation and sustained cellular proliferation. MAPK and parallel oncogenic pathways, including PI3K/AKT and receptor tyrosine kinases (EGFR, IGF-1R, and FGFR), function synergistically to enhance signaling redundancy and compensatory survival mechanisms. Therapeutic interventions targeting MAPK signaling-ranging from small-molecule inhibitors to RNA-based therapies-offer promising avenues for overcoming tamoxifen resistance.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132572","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":"Human TLS DNA polymerase: saviors or threats under replication stress?","authors":"Yogendra Singh Rajpurohit, Mitu Lal, Dhirendra Kumar Sharma, Ishu Soni","doi":"10.1007/s11010-025-05291-2","DOIUrl":"https://doi.org/10.1007/s11010-025-05291-2","url":null,"abstract":"<p><p>The maintenance of genomic stability is crucial for life, threatened by DNA damage from both endogenous and exogenous sources. Cells employ DNA damage response through various repair mechanisms and DNA damage tolerance via translesion synthesis (TLS), to bypass DNA lesions and prevent replication fork collapse. This review explores the roles of human TLS polymerases in navigating replication stress, a critical process that can lead to genomic instability and cancer. It discusses TLS polymerase's dual role in genome preservation under certain physiological conditions while may also contribute to adaptive mutagenesis, highlighting their significance in DNA damage tolerance, somatic hypermutations, and cancer therapeutics. Understanding these mechanisms offers insights for developing targeted cancer therapies.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128343","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":"YTHDC1 orchestrates oncogenic splicing via the CLK1-SRSF1 splicing machinery to regulate castration-resistant prostate cancer progression.","authors":"Parth Gupta, Devesh Srivastava, Vinayak Nayak, B Vishal Rao, K Suseela, Rakesh Sharma, Senthil J Rajappa, T Subramanyeshwar Rao, Parul Mishra, Ashish Misra","doi":"10.1007/s11010-025-05302-2","DOIUrl":"https://doi.org/10.1007/s11010-025-05302-2","url":null,"abstract":"<p><p>Androgen receptor variant 7 (AR-V7) plays a critical role in castration-resistant prostate cancer (CRPC) progression even under androgen-deprivation conditions. Clinical and experimental studies have established that AR-V7 expression is a critical driver of CRPC progression and resistance to first-line anti-androgen therapy including enzalutamide. Understanding the mechanisms regulating AR-V7 generation and its contribution to drug resistance is critical for developing newer approaches to target CRPC. In this study, we have investigated the role of the RNA-binding protein YTHDC1, a m6A reader, in regulating AR-V7 splicing. Our findings reveal that YTHDC1 is overexpressed in CRPC and modulating its expression directly affects AR-V7 levels, rendering the cells sensitive to enzalutamide treatment. Mechanistically, we demonstrate that YTHDC1 binds to the AR-V7 pre-mRNA and facilitates the recruitment of phosphorylated SRSF1, a splice factor that promotes AR-V7 splicing. Additionally, we also demonstrate that it modulates the levels of CLK1, a known SRSF1 kinase supporting its role in regulating AR-V7 splicing. Furthermore, our experiments also reveal that YTHDC1 regulates the expression of other oncogenic transcripts, including Bcl-2, Cyclin D1, Nova1, and VEGF-A, highlighting its broader role in cancer progression. Overall, our study supports that targeting YTHDC1 could be a novel therapeutic approach to overcome AR-V7-mediated treatment resistance in CRPC patients.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128348","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":"Exploring the therapeutic potential of annexin A1-derived peptide Ac_2-26 in modulating NLRP3 inflammasome activation in Crohn's disease.","authors":"Izabella Lice, Henrique T K Ito, Rebeca D Correia-Silva, Diego D Santos, Gisela R S Sasso, Paulo C Franco, Ricardo Artigiani, Karin V Greco, Cristiane D Gil","doi":"10.1007/s11010-025-05311-1","DOIUrl":"https://doi.org/10.1007/s11010-025-05311-1","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD) remains a complex and multifaceted condition, with its management dependent on a thorough understanding of its underlying mechanisms. While the ANXA1-FPR axis is implicated in the pathogenesis of IBD, its relationship with the NLRP3 inflammasome in this context has not been established. Thus, this study aimed to elucidate the intricate relationship between ANXA1, FPRs, and the NLRP3 inflammasome in the pathogenesis of IBD. For this purpose, mRNA and protein expression of ANXA1, FPRs, and NLRP3 inflammasome were analyzed using transcriptomic data (GSE179285) and immunohistochemistry on ileum and colon samples from CD patients and healthy controls. In vitro, ANXA1-derived peptide Ac_2-26's effect was tested on TNF-α-activated Caco-2 cells. Transcriptome analysis of GSE179285 revealed significantly increased levels of ANXA1, FPR1, FPR2, and NLRP3 transcripts in inflamed CD segments compared to controls. Immunohistochemistry confirmed these findings, showing strong immunoreactivity for ANXA1, FPR2, and NLRP3 in CD samples, particularly in the intestinal epithelium and inflammatory infiltrate. In vitro, ANXA1 and NLRP3 were co-expressed in Caco-2 cells stimulated with TNF-α. The peptide Ac_2-26 at 2 ng/mL significantly increased caspase-1 and IL-1β levels, enhancing NLRP3 inflammasome activation. Ac_2-26 also reduced ROS production and preserved epithelial integrity by enhancing occludin and cadherin expression. Overall, this study highlights the crucial role of ANXA1-FPR axis in regulating inflammation in CD and its potential therapeutic implications. Ac_2-26 modulates NLRP3 inflammasome activation and oxidative stress, preserves epithelial barrier integrity, and shows promise as a therapeutic target for IBD treatment.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111408","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":"Disease-modifying effect of donepezil on APP/PS1 mice at different stages of Alzheimer's disease.","authors":"Irina Zueva, Grigory Belyaev, Konstantin Petrov","doi":"10.1007/s11010-025-05310-2","DOIUrl":"https://doi.org/10.1007/s11010-025-05310-2","url":null,"abstract":"<p><p>Despite Alzheimer's disease (AD) representing a significant global health concern, disease-modifying therapeutic options remain elusive. The use of animal models of the disease to develop drugs intended for the treatment of AD does not always predict their efficacy in clinical trials. Our research demonstrates the benefits of a drug-withdrawal approach to screening AD-modifying compounds, focussing on β-amyloid (Aβ)-related pathological changes in APP/PS1 transgenic mice at different stages of the disease. To assess the efficacy of this approach, we examined the AD-modifying effect of donepezil as a reference drug. A significant cognitive decline exhibited by APP/PS1 transgenic mice from 8.4 months of age was accompanied by progressive accumulation of Aβ plaques, decreased synaptophysin and vesicular acetylcholine transporter immunoexpression. Donepezil had a disease-modifying effect, slowing the deterioration of all the pathological markers studied when treatment was started in a pre-symptomatic stage of AD. However, in the group of mice with advanced stage of AD, such disease-modifying effects were not evident.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120275","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":"Risk factors for cognitive decline in type 2 diabetes mellitus adults: a systematic review and meta-analysis.","authors":"Shengcheng Mao, Yingmin Wang","doi":"10.1007/s11010-025-05306-y","DOIUrl":"https://doi.org/10.1007/s11010-025-05306-y","url":null,"abstract":"<p><p>Cognitive decline (CD) is a common disorder in patients with type 2 diabetes mellitus (T2DM), which is affected by various factors. The present study aimed to investigate the factors affecting its occurrence CD in patients T2DM. The PubMed, Web of Science, Scopus, and Embase databases were searched for pertinent research on the risk factors for the beginning of CD. The remaining studies were assessed using predetermined inclusion and exclusion criteria after duplicate studies were eliminated. The Comprehensive Meta-Analysis software (version 2) was used to analyze the data. The Egger test and Begg and Mazumdar test was used to examine publication bias, while the I-square statistic was used to evaluate study heterogeneity. 95% confidence limits and odds ratios were used in the analysis. 40 studies were authorized for assessment and statistical analysis using the systematic review procedure. These studies' findings indicate that, using both crude and adjusted analyses, the odds ratio for the occurrence of CD in people with diabetes is higher for factors like low educational attainment, men, abnormal Hemoglobin A1c (HbA1C) levels, physical inactivity, depression, and stroke. Factors like low education, abnormal HbA1C levels, depression, and stroke as well increase the risk of developing CD in diabetic patients. These cases in diabetic patients require special attention.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120276","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":"The SIRT1/GPS2/AIP1 axis regulates pulmonary vascular permeability in ventilator-induced lung injury.","authors":"Yi Zhang, Cuicui Cao, Chang Sun, Jie Yan, Yuelan Wang, Changping Gu","doi":"10.1007/s11010-025-05313-z","DOIUrl":"https://doi.org/10.1007/s11010-025-05313-z","url":null,"abstract":"<p><p>Mechanical ventilation (MV) is essential for patients who require life support, but undue mechanical stress leads to airway and alveolar injury, also known as ventilator-induced lung injury (VILI). MV induces changes in pulmonary endothelial barrier integrity by affecting cell junction proteins. The mechanisms of disruption of endothelial barrier integrity during VILI are still unclear. This study aimed to investigate the roles and mechanisms by which ASK1-interacting protein-1 (AIP1), G-protein pathway suppressor 2 (GPS2), and sirtuin 1 (SIRT1) affect VILI. Human lung microvascular endothelial cells (HLMVECs) were transfected with AIP1 small interfering RNA (siRNA), GPS2 siRNA, GPS2 cDNA, and SIRT1 siRNA and subjected to 20% cyclic stretch (CS). C57BL/6N mice were pretreated with the SIRT1 siRNA before MV. We found that CS of 20% activated oxidative stress, increased the reactive oxygen species (ROS) production, and disrupted the pulmonary endothelial cell barrier integrity. AIP1 depletion increased the ROS production and aggravated the disruption of endothelial barrier integrity. Loss of GPS2 decreased the level of AIP1, leading to low expression levels of cell junction proteins. These effects were alleviated by GPS2 overexpression. SIRT1 depletion induced a decrease in GPS2 and AIP1, and increased the ROS production, resulting in decreased expression levels of cell junction proteins. Furthermore, VILI was exacerbated by increased cytokine production (IL-6 and IL-1β), pulmonary oedema, and an elevated wet/dry weight ratio in SIRT1-depleted mice under MV. These results suggest that cyclic mechanical stretching activated oxidative stress and disrupted the expression of cell junction proteins. The SIRT1/GPS2/AIP1 axis influences the production of ROS to regulate the pulmonary endothelial cell barrier integrity during VILI.</p>","PeriodicalId":18724,"journal":{"name":"Molecular and Cellular Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111353","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}