Biochemistry and Biophysics Reports最新文献

{"title":"Regulation of ferroptosis in colorectal cancer through therapeutic modulation and miRNA targeting","authors":"Ali Ahmadizad Firouzjaei ,&nbsp;Seyed Hamid Aghaee-Bakhtiari ,&nbsp;Samira Mohammadi-Yeganeh","doi":"10.1016/j.bbrep.2026.102444","DOIUrl":"10.1016/j.bbrep.2026.102444","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a highly prevalent disease that represents a major global health burden. Ferroptosis has gained significant attention in recent years as a potential target for cancer therapy. Meanwhile, microRNAs (miRNAs) have emerged as key regulators of gene expression, with the potential to influence various cellular pathways and functions, including those involved in cancer development and treatment. In this study, we employed a systems biology approach to leverage the FerrDb database and to identify key genes involved in the ferroptosis pathway. Then, we utilized the NCBI Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) associated with ferroptosis in CRC. The miRNet platform was used to identify miRNAs that target ferroptosis-associated genes in CRC. Additionally, we explored the Therapeutic Target Database (TTD) and Drug Gene Interaction Database (DGIdb) to identify approved drugs that could potentially modulate the identified targets. Our analysis identified <em>EZH2, G6PD, PARP1, RRM2, SCD</em>, and <em>SLC7A11</em> as key suppressor genes that are dysregulated in CRC and are also recognized as approved drug targets. Furthermore, we identified hsa-miR-423-5p, hsa-miR-93-5p, hsa-miR-15a-5p, miR-103a-3p, and hsa-miR-16-5p as the five top miRNAs that show the highest number of connections to genes involved in the ferroptosis pathway. Interestingly, we also found that medications such as prasterone, tazemetostat, isoxyl, gemcitabine, ponsegromab, scx-2023, and nicotinamide could potentially be used in combination with the identified miRNAs to target ferroptosis in CRC. To further validate the stability and reliability of the predicted protein–ligand interactions, molecular dynamics (MD) simulations and MM-PBSA analyses were performed on selected top-ranking complexes, which confirmed their stable and favorable binding and supported the robustness of our docking results. These findings suggest that targeting these miRNAs and their associated genes, along with using the identified drugs, could be a promising strategy for CRC treatment, leveraging the potential of ferroptosis-inducing therapies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102444"},"PeriodicalIF":2.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methanogenic activities signatures in broilers fed black soldier fly (Hermetia illucens) larvae-based diets","authors":"Deborah Oluwaferanmi Ibiwoye ,&nbsp;Opeyemi Adetola Oladejo ,&nbsp;Oluwatomisin Aderonke Akinsola ,&nbsp;Aruna Olasekan Adekiya ,&nbsp;Olufemi Mobolaji Alabi ,&nbsp;Ayantade Dayo Ayansina ,&nbsp;Samuel Olatunde Dahunsi","doi":"10.1016/j.bbrep.2026.102441","DOIUrl":"10.1016/j.bbrep.2026.102441","url":null,"abstract":"<div><div>Methanogenic archaea in the avian gut contribute to hydrogen turnover and thus play a role in fermentative efficiency and greenhouse gas emission. While black soldier fly larvae meal (BSFLM) has been explored as a replacement for fishmeal in broiler diets, less is known about how varying BSFLM inclusion levels affect methanogenesis pathways and enzyme activities in the gut microbial community. This study investigated the presence, relative abundance, and shifts in methanogenesis enzyme pathways in broilers fed diets with increasing levels of BSFLM. Arbor Acre Plus broiler chicks were allocated to five dietary treatments over 8 weeks. Diets replaced fishmeal with BSFLM at 0 % (control), 25 %, 50 %, 75 %, and 100 % levels. Cecal samples were collected post-mortem, DNA extracted, and the bacterial 16S rRNA (V1–V9) region sequenced on PacBio Sequel IIe. Functional predictions via PICRUSt2 were used to identify KEGG orthologs associated with methanogenesis (e.g. K00200–K00205 for FMD, K00399 etc. for MCR, methyltransferases, etc.). Enzyme detection across treatments was assessed qualitatively and semi-quantitatively (e.g. “low”, “moderate”, “strong”) based on relative abundance. Key methanogenic enzymes (including FMD, MCH, MTD, F420-dependent enzymes, methyltransferases, and MCR) were profiled, and their activity compared across treatments. Correlations were examined and predicted functional capacity via PICRUSt2. Methanogenesis-related pathways were detectable in all dietary treatments. In the control (0 % BSFLM), enzyme levels were minimal, reflecting low background methanogenic potential. At 25 % BSFLM inclusion (T2), there was strong detection of hydrogenotrophic pathway enzymes (FMD, coenzyme F420 hydrogenase, MCR) and moderate presence of methylotrophic methyltransferases, suggesting dominance of hydrogenotrophic methanogenesis. In the 50 % BSFLM treatment (T3), enzyme levels declined somewhat: hydrogenotrophic enzyme activity was moderate, and methylotrophic components were weaker. With 100 % BSFLM (T5), methylotrophic pathway enzymes (methanol- and methylamine-corrinoid protein Co-methyltransferases) were strongly detected, while hydrogenotrophic enzymes persisted but at low levels. These shifts have implications for gut fermentation efficiency, substrate (hydrogen and methyl compound) availability, nitrogen metabolism, and possibly GHG emission. Optimization of BSFLM inclusion levels may help balance production performance and environmental sustainability.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102441"},"PeriodicalIF":2.2,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological functions of tsRNAs and research advances in human disease","authors":"Yanting Jiang ,&nbsp;Shuyou Liu ,&nbsp;Guolin Li ,&nbsp;Chengcheng Tang ,&nbsp;Yangyang Zhang ,&nbsp;Junjie Li ,&nbsp;Zhirong Tan ,&nbsp;Shimeng Zhang ,&nbsp;Zhiyou Chen ,&nbsp;Shulong Li","doi":"10.1016/j.bbrep.2025.102438","DOIUrl":"10.1016/j.bbrep.2025.102438","url":null,"abstract":"<div><div>tsRNAs (tRNA-derived small RNAs) are a class of noncoding small RNAs generated by nuclease-specific cleavage of mature tRNAs or their precursors. Since their functional discovery in 2009, tsRNAs have emerged as a research hotspot in molecular biology and medicine because of their unique generation mechanism, tissue-specific expression patterns, and diverse regulatory functions. Compared with traditional non-coding RNAs (such as miRNAs and lncRNAs), tsRNAs exhibit distinct biological activities in stress responses, translational regulation, and epigenetic modifications and are closely associated with the onset and progression of various human diseases. This systematic review covers the discovery history, classification characteristics, primary biological functions, and action mechanisms of tsRNAs in major diseases, including respiratory disorders, neuropsychiatric conditions, cardiovascular diseases, and tumors. It further explores the clinical translational potential of tsRNAs as disease biomarkers and therapeutic targets, identifies current challenges, and outlines future research directions. Major knowledge gaps highlighted include the lack of standardized detection methods for tsRNA subtypes, unclear specificity of their molecular targets in pathological processes, and limited validation in large clinical cohorts; key challenges involve inefficient delivery of tsRNA-based therapeutics and insufficient exploration of cross-species conservation. The review aims to provide a comprehensive reference for in-depth studies in the field of tsRNA.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102438"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular crosstalk between AHR, CYP1B1, and ITGAM in diabetic nephropathy: Integrated insights from bioinformatics and experimental validation","authors":"Seyed Amirhossein Hosseini ,&nbsp;Parisa Ajorlou ,&nbsp;Pegah Mousavi ,&nbsp;Sepideh Aghamirli ,&nbsp;Aghdas Dehghani","doi":"10.1016/j.bbrep.2025.102422","DOIUrl":"10.1016/j.bbrep.2025.102422","url":null,"abstract":"<div><div>Chronic inflammation and a progressive loss of kidney function are hallmarks of diabetic nephropathy (DN). Th22 cells are mainly regulated by the transcription factor AHR, which is essential for their differentiation and inflammatory responses. This study aims to investigate the regulatory role of Th22 cells in the progression of DN. The GEO database was used to retrieve the GSE142025 (DN) and GSE135390 (Th22) datasets, which provided transcriptomic profiles for gene expression analysis. WGCNA was employed to identify gene co-expression modules strongly correlated with DN progression. Gene expression levels were validated by real-time PCR in 90 PBMC samples (30 per group: T2DM, DN, and healthy controls). Gene–drug interactions were subsequently predicted using the DGIdb database. In DN, 4006 differentially expressed genes (DEGs) were identified, while 831 DEGs were detected in Th22 cells. After intersecting these DEGs using a Venn diagram tool, 106 common genes were found. Following the construction of a protein-protein interaction network using the STRING database and subsequent analysis in Cytoscape, ITGAM was identified as the central hub gene. Real-time PCR analysis demonstrated significantly elevated expression levels of AHR (a major transcription factor of Th22 cells), ITGAM, and CYP1B1 (a downstream target gene of AHR) in DN patients compared to those with T2DM and healthy controls. Changes in the transcript levels of ITGAM, CYP1B1, and AHR were associated with renal biochemical parameters. Additionally, 60 drugs were predicted to regulate AHR, 12 targeted ITGAM, and 33 targeted CYP1B1. This study highlights the potential role of AHR, ITGAM, and CYP1B1 in the pathogenesis of DN. Their altered expression patterns suggest they could serve as useful biomarkers for monitoring disease progression.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102422"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis and characterization of a novel metallophosphoesterase from Akkermansia muciniphila involved in lipid degradation","authors":"Miao Guan ,&nbsp;Lei Li ,&nbsp;Yang Zheng ,&nbsp;Shaoxing Dai ,&nbsp;Runling Wei ,&nbsp;Zhenglong Sun","doi":"10.1016/j.bbrep.2025.102437","DOIUrl":"10.1016/j.bbrep.2025.102437","url":null,"abstract":"<div><div>Gut microbes play an important role in the regulation of host health. Multiple studies have shown that <em>Akkermansia muciniphila</em>, as a promising beneficial gut bacterium, is robustly associated with positive effects on host metabolism, immunological regulation, and its presence inversely correlates with body weight. But the precise function played by this bacterium underlying lipid degradation is still unknown. Here we identify a metallophosphoesterase from <em>A. muciniphila.</em> The metallophosphoesterase is composed of a binuclear metal center connected with tyrosine residues and a highly conserved calcineurin-like_PHP_ApaH domain. The enzyme activity has reached its peak in the conditions of pH 8.0, temperature of 37 °C. The enzyme is active for esters with short fatty-acid chains, and has high catalytic activity for hydrolysis of phospholipid sodium salts. In addition, five of predicted active sites of the metallophosphoesterase affecting its enzymatic activity are individually analyzed. Point mutation of H47 reduces the catalytic activity of the metallophosphoesterase for its most preferred substrate, while mutation of H181 has the opposite effect of increasing the enzymatic activity. Overall, we report the first characterization of AMUC-1901, a novel metallophosphoesterase from <em>A. muciniphila</em> with lipid degradation capabilities, which has potential for further exploration in developing novel food or pharma supplements for obesity therapies.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102437"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of myocardial microcirculation changes in rats from different altitudes based on CT myocardial perfusion imaging","authors":"Chunlong Yan ,&nbsp;Jinfeng Ma ,&nbsp;Tingjun Yan ,&nbsp;Yanqiu Sun","doi":"10.1016/j.bbrep.2025.102417","DOIUrl":"10.1016/j.bbrep.2025.102417","url":null,"abstract":"<div><div>This study employed computed tomography myocardial perfusion imaging (CT-MPI) to investigate myocardial microcirculation changes in rats across different altitudes. Four-week-old male Sprague-Dawley rats were allocated into plain (450 m), moderate-altitude (MA, 2200 m), and high-altitude (HA-A, 3800 m; HA-B, 4200 m) groups. After 28 weeks, CT-MPI revealed significant altitude-dependent alterations in myocardial perfusion parameters: TTP and MTT increased while BF and BV decreased (P &lt; 0.05). Accompanying these changes were modifications in blood parameters—including red blood cell indices, white blood cell counts, and biochemical markers—along with myocardial structural remodeling characterized by disordered cell arrangement, widened intercellular gaps, and increased collagen deposition. Molecular analyses demonstrated variations in mRNA and protein expression of hypoxia-related markers (CD34, EPO, VEGF, HIF-1α, HIF-2α) and collagen types I/III, with HIF-2α exhibiting particular sensitivity to altitude variation. These findings indicate that high-altitude exposure induces progressive myocardial microcirculation impairment coupled with hematological adaptations and tissue remodeling, potentially mediated through HIF-2α-regulated hypoxia response pathways.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102417"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating psychological stress-induced cardiac injury: The impact of CB2R agonists on endoplasmic reticulum stress and mitophagy","authors":"Chenke Ma ,&nbsp;Wenbin Gai ,&nbsp;Kan Zhang ,&nbsp;Cheng Qin","doi":"10.1016/j.bbrep.2025.102425","DOIUrl":"10.1016/j.bbrep.2025.102425","url":null,"abstract":"<div><h3>Background</h3><div>Psychological stress is a recognized contributor to cardiac injury and disease; however, the molecular mechanisms underlying this relationship remain incompletely understood, and effective therapeutic strategies are still limited.</div></div><div><h3>Materials and methods</h3><div>DEGs were identified from our sequencing data and GEO datasets, intersected with ER stress/mitophagy-related genes, and then prioritized by machine-learning and network analyses; pathway activity, immune signatures, molecular subtypes, and miRNA–mRNA interactions (DIANA-TarBase) were further characterized and experimentally validated.</div></div><div><h3>Results</h3><div>In cardiac injury induced by psychological stress, 38 differentially expressed ER stress- and mitophagy-related genes were identified. Through methods such as LASSO regression, four key genes—Foxo3, Pparg, Sirt1, and Stat3—were selected. ROC analysis of the four-gene phenotype score showed strong discrimination in the test dataset (AUC = 0.917 for control vs. stress; AUC = 0.938 for stress vs. CB2R-agonist treatment) and moderate discrimination in the external validation cohort GSE68077 for the comparison of controls versus 5dayStress-1dayRest samples (AUC = 0.720). Correlation analysis revealed that Sirt1 exhibited significant positive correlations with CD56bright natural killer cells, MDSCs, and Type 1 T helper cells. Pparg showed a notable positive association with Type 1 T helper cells, while γδ T cells showed significant negative correlations with Stat3, Sirt1, Pparg, anRd Foxo3. Treatment with a cannabinoid type 2 receptor (CB2R) agonist notably downregulated the expression of these four key genes.</div></div><div><h3>Conclusion</h3><div>This study provides mechanistic insight into molecular processes underlying psychological stress–induced cardiac injury. The identified four-gene module may serve as an exploratory molecular signature and a starting point for evaluating CB2R agonism as a modulator of ER stress and mitophagy.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102425"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8-O-acetylharpagide, an active compound isolated from A. taiwanensis selectively induced G2/M phase arrest and radiosensitivity in hypopharyngeal cancer cells","authors":"Wan-Yu Yang ,&nbsp;Yung-Cheng Wang ,&nbsp;Yun-Lian Lin ,&nbsp;Kuei-Yuan Hou ,&nbsp;Wan-Chun Li ,&nbsp;Yi-Jang Lee","doi":"10.1016/j.bbrep.2025.102431","DOIUrl":"10.1016/j.bbrep.2025.102431","url":null,"abstract":"<div><div>Hypopharyngeal cancer (HPC) is a rare but most malignant subtype of head and neck squamous cell carcinoma (HNSCC). Conventional chemo-radiotherapy is the primary approach for the treatment of HPC, while the efficacy is limited and complications. Previously, we have isolated an active compound (AT-1) identified as 8-O-acetylharpagide from <em>Ajuga taiwanensis</em>. Because Ajuga extracts are both edible and known for their anti-cancer properties, it is worthwhile to investigate whether AT-1 can inhibit cancers of otolaryngological origin. In this study, we compared the cell killing effects of AT-1 on FaDu HPC cells and periodontal ligament <em>(</em>PDL) cells. The results showed that AT-1 was more toxic on FaDu cells (IC₅₀ = 0.88 mM) than on PDL cells (IC₅₀ = 1.65 mM), yielding a selectivity index (SI) ≈ 1.85. AT-1 caused significant G2/M phase arrest in FaDu cells with a dose-dependent manner. Concomitantly, high concentration of AT-1 could induce necrosis-like fraction and late apoptosis in FaDu cells. Notably, AT-1 did not influence the cell cycle redistribution and cell death in PDL cells under the same condition of treatment. Furthermore, AT-1 enhanced the radiosensitivity of FaDu cells rather than PDL cells, suggesting that AT-1 induced G2/M phase arrest remains sensitive to ionizing radiation known as a principle of radiobiology. Taken together, current data indicate that AT-1 raises selectively efficacy on HPC cells by increasing G2/M phase arrest, apoptosis, as well as radiosensitivity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102431"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SERPINA3 facilitates malignant progression and remodels tumor immune microenvironment in glioma","authors":"Wanwan Wen ,&nbsp;Qing Zhang","doi":"10.1016/j.bbrep.2025.102419","DOIUrl":"10.1016/j.bbrep.2025.102419","url":null,"abstract":"<div><div>Glioblastoma (GBM) have high aggression and immunosuppression characteristics, with treatment limitation and poor clinical prognosis. Glioma-associated macrophages and microglia (GAMs) constitute the majority immune cells in the tumor microenvironment (TME). Differential molecular characteristics in GBM are related to the poor prognosis and result in therapeutic resistance. Previous research revealed that elevated SERPINA3 expression portends a dismal prognosis for glioma patients. However, the relationship between SERPINA3 and glioma malignant progression, as well as its association with GAMs infiltration, remains unclear. In this study, we explored SERPINA3 levels in different grade glioma tissues and its correlation with GAMs markers. We found that an upregulated of SERPINA3 protein expression in GBM tissues compared to low-grade gliomas. Notably, the expressions of CD68 and IBA1, markers for GAMs, were significantly increased in GBM. Furthermore, we observed a strong correlation between high levels of SERPINA3, CD68, and IBA1 with reduced survival in patients with primary gliomas. Intriguingly, within GBM tissues, we further confirmed the expression of SERPINA3 in GAMs, and that SERPINA3 expression is positively associated with CD68 and IBA1 in primary gliomas, indicating remodeling of the tumor immune microenvironment. This study provides an insight into the therapeutic strategy targeting SERPINA3 in glioma patients.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102419"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational analysis of the structural and functional impact of the deleterious nsSNPs in the human F2R gene and their implications in glioma","authors":"Saif Mukramoon Arosh ,&nbsp;Md. Raiyan Hosen ,&nbsp;Md. Ismail Hosen ,&nbsp;Atiqur Rahman","doi":"10.1016/j.bbrep.2025.102430","DOIUrl":"10.1016/j.bbrep.2025.102430","url":null,"abstract":"<div><div>The protease-activated receptor 1 (PAR1) protein, derived from the <em>F2R</em> gene, is integral to various physiological and pathological mechanisms and has been recognized as an oncogene in multiple studies, playing a crucial role in the aggressive and metastatic characteristics of cancer. However, no comprehensive investigation has yet been conducted on the possible impact of its missense mutations. In this study, we employed a computational pipeline to determine potentially deleterious nonsynonymous single-nucleotide polymorphisms (nsSNPs) within the <em>F2R</em> gene and evaluate their structural and functional impact on the PAR1 protein, as well as their association with cancer. PAR1 missense variants were primarily retrieved from the dbSNP database and Ensembl genome browser. Fifteen variants were subsequently predicted to exert detrimental effects using fourteen different computational tools. Phenotypic effect prediction, integrated with structural modeling, revealed that two variants (R214H and C378G) exert the most severe functional consequences, based on their location in highly conserved regions and their predicted ability to destabilize protein structure. Molecular docking analysis and subsequent molecular dynamics simulations demonstrated a destabilization of the two variants compared to the wild type, potentially leading to reduced protein activity. Furthermore, non-coding SNPs were predicted to alter regulatory elements of the <em>F2R</em> gene, influencing its expression across multiple tissues. Analysis of the <em>F2R</em> gene using TCGA data suggested its significant association with the progression and overall survival of low-grade glioma patients. These findings provide a foundation for future large-scale population studies and highlight the prospect of targeting PAR1 protein variants in cancer research and drug discovery, particularly in the context of precision medicine for glioma.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102430"},"PeriodicalIF":2.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}