Archives of biochemistry and biophysics最新文献

{"title":"LncRNA SNHG15 facilitates the advancement of preeclampsia via the miR-451a/ATF2 axis.","authors":"Min Wu, Jing Li, Xiaoqian Fu, Xiujing Lu, Lu Xiao, Yachang Zeng","doi":"10.1016/j.abb.2025.110570","DOIUrl":"10.1016/j.abb.2025.110570","url":null,"abstract":"<p><p>Preeclampsia (PE) is a pregnancy complication that poses a major risk to both the maternal and the fetal's safety. By studying the role and mechanism of LncRNA SNHG15 in preeclampsia pathogenesis, this study aimed to better understand the pathophysiology and prevention of PE. Placental samples and hypoxic trophoblast cell line--HTR8/SVneo were analyzed using qPCR to determine the differential expression of LncRNA SNHG15. Nuclear-cytoplasmic fractionation assays confirmed that LncRNA SNHG15 is predominantly localized in the cytoplasm of HTR8/SVneo cells, where it modulates cellular functions including proliferation, migration, and invasion. Using a dual luciferase reporter assay and rescue experiment, functions of miRNA-451a and LncRNA SNHG15 in HTR8/SVneo cells were examined. ATF2 expression levels in the hypoxic cell model and after LncRNA SNHG15 and miR-451a interference were confirmed by qPCR and Western blot. Evidence from this study indicates that LncRNA SNHG15 may be involved in the onset of preeclampsia, suggesting its viability as a novel treatment target.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110570"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768319","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":"Galectin-8 binding to alpha-1 antitrypsin is a physiological mechanism in healthy individuals but exacerbates the symptoms of alpha-1 antitrypsin deficiency.","authors":"Hend Sayed, Kevin H Mayo, Yifa Zhou, Guihua Tai, Jiyong Su","doi":"10.1016/j.abb.2025.110577","DOIUrl":"10.1016/j.abb.2025.110577","url":null,"abstract":"<p><p>Alpha-1 Antitrypsin (AAT) is a serine protease inhibitor that protects lung tissue by neutralizing neutrophil elastase. Galectin-8 (Gal-8) is a tandem-repeat galectin with N- and C-terminal carbohydrate recognition domains (CRDs) that bind β-galactoside-containing N-glycans. Both proteins co-localize in pulmonary and circulatory systems, suggesting a physiological interaction. Here, we demonstrate a glycan-dependent binding between Gal-8 and AAT using pull-down assays, mass spectrometry, isothermal titration calorimetry, and size-exclusion chromatography. Importantly, binding of Gal-8 impairs AAT's protease inhibitory activity, with the N-terminal CRD of Gal-8 sufficient to disrupt AAT function. Kinetic analyses show that Gal-8 inhibits AAT and enhances trypsin activity, as evidenced by a decrease in K_m and an increase in catalytic efficiency (k_cat/K_m). In cell assays, Gal-8 restored trypsin-mediated proteolysis and induced cell detachment in HeLa and CHO cells despite AAT presence, confirming biological relevance. Leveraging this interaction, we developed a lactose-mediated elution method to purify AAT from human and bovine serum using Gal-8 immobilized on Ni-NTA beads. Moreover, a stable CHO cell line expressing recombinant AAT (∼2 g/L) exhibited glycosylation comparable to serum AAT and retained Gal-8 binding. Our findings reveal Gal-8 as a novel modulator of AAT activity and present a glycan-specific strategy for AAT purification, with implications for biotherapeutic production and quality control.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110577"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803286","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":"β-Galactosidase inhibition explored by biochemical methods and in silico studies for plant polyphenols.","authors":"Ahmed Zayed, Karima Sayah, Kalicharan Sharma, Rasha Ali Radwan, Shahira M Ezzat","doi":"10.1016/j.abb.2025.110568","DOIUrl":"10.1016/j.abb.2025.110568","url":null,"abstract":"<p><p>β-Galactosidase is a lysosomal enzyme whose deficiency is associated with genetic disorders such as GM1 gangliosidosis, prompting the search for novel enzyme modulators with therapeutic potential. The current study evaluated the inhibitory potential of selected natural polyphenols against β-galactosidase using a combined approach of biochemical assays and computational modeling. Sixteen plant-derived compounds were initially screened through molecular docking against Aspergillus oryzae β-galactosidase. Among these, hesperidin, rutin, and chlorogenic acid exhibited the most favorable interactions and were subsequently assessed through in vitro enzyme inhibition assays and MM/GBSA binding energy calculations. These compounds showed potential inhibitory effects and stable binding within the enzyme's active site. Although classical pharmacological chaperone activity was not directly demonstrated, the observed modulation of enzyme function suggests potential for further development of these polyphenols as structurally distinct β-galactosidase inhibitors. The findings provide a basis for future investigations aimed at natural product-based strategies to manage lysosomal storage disorders such as GM1 gangliosidosis.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110568"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726937","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":"TNF promotes osteoclastogenesis by secreting miR-31-5p into small extracellular vesicles via the autotaxin–LPA–LPAR1 axis in arthritic fibroblast-like synoviocytes","authors":"Thanh Nam Phan ,&nbsp;Minju Gal ,&nbsp;Okhwa Kim ,&nbsp;Hoang Long Le ,&nbsp;Cheol Hwangbo ,&nbsp;Jeong-Hyung Lee","doi":"10.1016/j.abb.2025.110631","DOIUrl":"10.1016/j.abb.2025.110631","url":null,"abstract":"<div><div>Fibroblast-like synoviocytes (FLSs) play a crucial role in the pathogenesis of arthritis. However, the impact of small extracellular vesicles (sEVs) secreted by FLSs on osteoclastogenesis remains incompletely understood. In this study, we aimed to investigate the role of tumor necrosis factor (TNF)- and lysophosphatidic acid (LPA)-activated FLSs in sEV-mediated release of osteoclastogenic miRNAs and elucidate their functional contribution to osteoclastogenesis. Stimulation of SW982 cells with LPA or TNF significantly increased sEV secretion. TNF upregulated autotaxin expression and promoted sEV release; however, small interfering RNA (siRNA)-mediated knockdown (KD) of <em>LPAR1</em> attenuated the increase in sEV release induced by the TNF–autotaxin–LPA axis. Notably, stimulation with TNF or LPA elevated syntenin-1 expression without altering its mRNA level. Furthermore, KD of the syntenin-1 gene (<em>SDCBP</em>) suppressed the LPA-induced increase in sEV release, indicating that syntenin-1 may mediate sEV secretion induced by the TNF–autotaxin–LPA–LPAR1 axis. sEVs derived from TNF- or LPA-treated SW982 cells stimulated osteoclastogenesis. We identified <em>miR-31-5p</em> as an osteoclastogenic miRNA enriched in sEVs. Expression levels of <em>miR-31-5p</em> in sEVs from TNF- and LPA-stimulated rheumatoid arthritis (RA) FLSs were significantly higher than in those from unstimulated RA FLSs. Treatment with a <em>miR-31-5p</em> mimic enhanced osteoclastogenesis by targeting large tumor suppressor kinase 2 (<em>LATS2</em>), whereas treatment with its inhibitor suppressed the sEV-mediated promotion of osteoclastogenesis. These findings reveal a mechanism by which TNF- and LPA-activated FLSs may facilitate sEV-mediated delivery of osteoclastogenic miRNAs, such as <em>miR-31-5p</em>, to osteoclast precursors, thereby contributing to osteoclast formation and bone destruction.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110631"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217861","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":"Human umbilical cord blood cells-secreted exosomal MFG-E8 regulates microglia polarization and ameliorates hypoxic-ischemic brain damage in neonatal rats by SOCS3/STAT3 axis","authors":"Yanhan Liu ,&nbsp;Menghua Zhao ,&nbsp;Ming Ling ,&nbsp;Mingyan Shen ,&nbsp;Furong Huang ,&nbsp;Jun Xu ,&nbsp;Duane Wang ,&nbsp;Aimin Zhang","doi":"10.1016/j.abb.2025.110629","DOIUrl":"10.1016/j.abb.2025.110629","url":null,"abstract":"<div><h3>Objective</h3><div>Stem cell therapy is expected to become a new treatment for central nervous system damage associated with perinatal hypoxic-ischemic encephalopathy (HIE), but the specific effects are unknown. This study explores the effects of human umbilical cord blood (HUCB) cells-secreted exosomal (HUCB-ex) MFG-E8 in neonatal rats with hypoxic-ischemic brain damage (HIBD), aiming to gain a theoretical foundation for the cure of perinatal HIE.</div></div><div><h3>Methods</h3><div>HIBD model was constructed in the Sprague Dawley rats (7-day-old). Rats were then intervened with 1 × 10⁶ HUCB cells, HUCB-ex, or HUCB-ex^oe-MFG-E8, and HUCB-ex^si-MFG-E8. Primary microglia from rats were induced with oxygen-glucose deprivation and re-oxygenation (OGD/R), then co-cultured with either HUCB or primary neuronal cells, and subjected to treatment with HUCB-ex, HUCB-ex^oe-MFG-E8, HUCB-ex^si-MFG-E8, or Stattic. The expression of polarization factors and secreted factors in the microglia was measured using RT-qPCR, immunofluorescence, and Western blot. Neuronal cell damage was assessed using MTT assays and flow cytometry. Behavioral impairments and brain tissue damage in the rats were evaluated using assays including the geotaxis reflex, cliff avoidance response, grip strength test, hematoxylin-eosin staining, TTC staining, and immunofluorescence.</div></div><div><h3>Results</h3><div>Early intervention with HUCB cells in HIBD rats increased test scores, decreased brain tissue weight, infarct area, as well as the IL-6, TNF-α, and IL-1β levels, and increased MFG-E8 levels. HUCB cells also decreased the levels of CD11b/c⁺CD45^hi cells in HIBD rat brain tissue, and increased the levels of CD206⁺CD11b/c⁺ cells. <em>In vitro</em> experiments confirmed high expression of MFG-E8 in HUCB-ex. HUCB-ex^si-MFG-E8 inhibited M2 polarization and induced neuronal cell injury through the SOCS3/STAT3 pathway. HUCB-ex and HUCB cells have equivalent therapeutic effects in HIBD rats. The treatment effectiveness of HUCB-ex was improved after delivering HUCB-ex^oe-MFG-E8, while was blocked after delivering HUCB-ex^si-MFG-E8.</div></div><div><h3>Conclusions</h3><div>HUCB-ex^oe-MFG-E8 promoted M2 polarization of microglial and inhibited neuronal cell apoptosis through the SOCS3/STAT3 pathway, to alleviate behavioral disorders and brain tissue damage in HIBD rats.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110629"},"PeriodicalIF":3.0,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190622","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 and functional identification of tyrosine hydroxylase in the yellow fever mosquito, Aedes aegypti","authors":"Xiaojing Zhu ,&nbsp;Linlong Jiang ,&nbsp;Xue Gong ,&nbsp;Jing Chen ,&nbsp;Yanhui Liu ,&nbsp;Pablo Sobrado ,&nbsp;Yingying Guo ,&nbsp;Qian Han","doi":"10.1016/j.abb.2025.110626","DOIUrl":"10.1016/j.abb.2025.110626","url":null,"abstract":"<div><div><em>Aedes aegypti</em>, an arthropod vector that transmits arboviral infectious diseases via blood feeding, has garnered significant attention. However, the in vitro biochemical activity of tyrosine hydroxylase (TH) in <em>Ae. aegypti</em> remains to be confirmed, and the functional role of this enzyme in mosquito has yet to be thoroughly elucidated. TH is a rate-limiting enzyme in the tyrosine metabolic pathway. Here, we identified the sequence and biochemical activity of TH in the mosquito, <em>Aedes aegypti</em>. To investigate the biological function of <em>TH</em> in the development of <em>Ae. aegypti</em>, RNA interference was used in the larvae and adults of <em>Ae. Aegypti</em>. The larvae were fed with chitosan-coated double stranded (ds) <em>Ae. aegypti TH</em> (<em>AeTH</em>) and adult mosquitoes were microinjected with <em>dsAeTH</em>. The number of pupae developed was decreased after <em>AeTH</em> knockdown in larvae, and the number of eggs laid, egg hatching rate, and blood intake of adult mosquitoes after <em>AeTH</em> knockdown were also decreased. The unhatched eggs laid had no normal larvae inside. The results here suggest that <em>AeTH</em> is involved in pupation and affects the normal development and fertility of the adults. The expression levels of melanization- and immune-related genes were examined. The results revealed that TH significantly affected bothmelanization and immune pathways. Collectively, these findings deepen our understanding of the functional role of TH in mosquitoes.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110626"},"PeriodicalIF":3.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181943","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":"SPP1-mediated crosstalk between macrophage and fibroblasts promotes benign airway stenosis","authors":"Fu Niu ,&nbsp;Bo Sun ,&nbsp;Ying Yu ,&nbsp;Xiaolan Xu ,&nbsp;Haitao Li ,&nbsp;Lining Huang ,&nbsp;Yan Wang ,&nbsp;Zhigang Cai","doi":"10.1016/j.abb.2025.110627","DOIUrl":"10.1016/j.abb.2025.110627","url":null,"abstract":"<div><h3>Objective</h3><div>The aim of this study is to elucidate the role of M2 macrophages in the pathogenesis of benign airway stenosis using a Sprague Dawley (SD) rat model and in vitro macrophage–fibroblast co-culture systems.</div></div><div><h3>Methods</h3><div>Ligand–receptor interactions mediating cellular crosstalk between macrophages and fibroblasts were identified through single-cell RNA sequencing-based bioinformatics analysis. An airway stenosis model was established in SD rats, which were assigned to five experimental groups: normal control and post-modeling days 1 (D1), 4 (D4), 7 (D7), and 14 (D14). Temporal changes in M2 macrophage infiltration and their involvement in airway remodeling were assessed. Fibroblasts isolated from human granulation tissue and normal airway tissue were evaluated for differential activation of intracellular signaling pathways. In vitro macrophage–fibroblast co-culture systems involving M2 macrophages and fibroblasts were conducted to assess molecular signaling interactions.</div></div><div><h3>Results</h3><div>A progressive increase in M2 macrophage infiltration was observed during the development of airway stenosis, accompanied by upregulation of secreted phosphoprotein-1 (SPP1) and activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Fibroblasts derived from granulation tissue exhibited higher levels of pathway activation compared to normal fibroblasts.In co-culture, M2 macrophages induced fibroblast activation and fibrogenesis via SPP1-mediated signaling. Administration of rapamycin, an mTOR pathway inhibitor, significantly reduced granulation tissue formation and improved airway patency in the rat model.</div></div><div><h3>Conclusion</h3><div>M2 macrophages contribute to fibrotic airway remodeling in benign airway stenosis through SPP1-mediated activation of the PI3K/AKT/mTOR signaling pathway in fibroblasts. Pharmacological targeting of this axis with rapamycin may represent a potential therapeutic strategy for mitigating fibrosis in benign airway stenosis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110627"},"PeriodicalIF":3.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181952","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":"“Single molecule tracking unveils distinct FcγRIIB and FcRn plasma membrane dynamics”","authors":"Marta Rojas-Rodríguez ,&nbsp;Francesco Saverio Pavone ,&nbsp;Martino Calamai","doi":"10.1016/j.abb.2025.110628","DOIUrl":"10.1016/j.abb.2025.110628","url":null,"abstract":"<div><div>Fc receptors (FcRs) constitute a heterogeneous family of membrane-bound proteins that are integral to the immune system function, primarily through their ability to bind the constant domain (Fc) of antibodies. These receptors mediate a variety of immunological processes and maintain immunological homeostasis. FcRs exhibit a broad distribution throughout the body, being expressed not only on the surface of various immune cells but also in non-immune cells and tissues. Over the past decade, specific FcRs -most notably the neonatal Fc receptor (FcRn) and Fc gamma receptor IIb (FcγRIIB)- have emerged as putative mediators in processes such as antibody-mediated uptake. However, the literature presents conflicting evidence regarding their precise roles and mechanisms in antibody internalization. In this study, we employed single molecule tracking in living epithelial-like cells to investigate the cellular distribution and dynamics of FcγRIIB and FcRn, basic features that are still largely uncharacterized. Our findings revealed that FcγRIIB, mostly present on the cell membrane, is highly mobile and can be actively internalized. Conversely, FcRn was primarily localized intracellularly, with only a minor fraction capable of reaching the cell surface, where it exhibited minimal mobility. These results show that FcγRIIB, but not FcRn, displays the basic expected requisites that would be necessary for surface antibody binding and uptake.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110628"},"PeriodicalIF":3.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184523","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":"Exosomal FGG promotes colorectal cancer liver metastases through inducing angiogenic pre-metastatic niche formation","authors":"Lingling Yang ,&nbsp;Lifang Chen ,&nbsp;Xin Chen ,&nbsp;Haiqiang Huang ,&nbsp;Hui Zhu ,&nbsp;Liangtao Zeng ,&nbsp;Jun Huang ,&nbsp;Hao Ding","doi":"10.1016/j.abb.2025.110625","DOIUrl":"10.1016/j.abb.2025.110625","url":null,"abstract":"<div><div>Angiogenesis is a defining feature of a pre-metastatic niche and is essential for primary colorectal cancer (CRC) tumor metastasis. Epithelial-mesenchymal transition (EMT) also serves as a critical driver of CRC tumor metastatic progression. Here, we hypothesized that exosomes from CRC cells promoted liver metastasis by remodeling tumor microenvironment. To verify this hypothesis, exosomes from CRC cells were isolated and identified, and the effects of these exosomes on human umbilical vein endothelial cells (HUVECs) were investigated. Exosomes from CRC cells promoted vascularization, permeability and migration of HUVECs. Mechanistically, exosomes derived from CRC cells delivered Fibrinogen gamma (FGG) to exert their effects on HUVECs. Furthermore, FGG downregulated the levels of VE-cadherin and E-cadherin in CRC cells, while upregulating N-cadherin and vimentin levels, thereby enhancing endothelial permeability and promoting EMT. <em>In vivo</em> experiments demonstrated that FGG downregulated VE-cadherin in CRC tissues and upregulated CD31 in liver tissues, ultimately leading to an increased number of metastatic liver nodules in a mouse model of CRC liver metastasis. In conclusion, FGG facilitates CRC liver metastasis by regulating key angiogenic, adhesion and mesenchymal markers via exosome-mediated mechanisms, resulting enhanced angiogenesis, vascular permeability, and EMT induction. These findings offer new insights into the mechanisms and treatment strategies of CRC liver metastasis.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110625"},"PeriodicalIF":3.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181890","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 of a circRNA-miRNA-mRNA ceRNA regulatory network identifies RNAs and genes linked to human ovarian clear cell carcinoma","authors":"Weidi Wang ,&nbsp;Chen Yang ,&nbsp;Jiayuan Zhao ,&nbsp;Xinghan Cheng ,&nbsp;Tianyi Chen ,&nbsp;Junjun Yang ,&nbsp;Yang Xiang","doi":"10.1016/j.abb.2025.110623","DOIUrl":"10.1016/j.abb.2025.110623","url":null,"abstract":"<div><h3>Background</h3><div>Ovarian clear cell carcinoma (OCCC) is an aggressive epithelial ovarian cancer subtype that prevalent in East Asia. Competing endogenous RNA (ceRNA) networks involving circular RNAs (circRNAs) and microRNAs (miRNAs) represent underexplored regulatory layers in OCCC pathogenesis.</div></div><div><h3>Methods</h3><div>Multi-omics integration of circRNA (GSE271851 and GSE266248) and miRNA (GSE230956 and GSE200852) datasets from GEO was performed using DESeq2 and limma tools (|log2FC|≥1, <em>p</em> &lt; 0.05). Experimentally validated circRNA-miRNA interactions were predicted using circBank 2.0, Circular RNA Interactome, and Starbase v3.0. ceRNA networks were constructed using inverse correlation principles and visualized in Cytoscape. Immune associations were assessed using TIMER2.0. Prognostic and expression validations were performed using the Kaplan-Meier Plotter and HPA databases, respectively.</div></div><div><h3>Results</h3><div>Three core circRNAs (hsa_circ_0002822, hsa_circ_0003641 and hsa_circ_0030509) were identified as being dysregulated across OCCC models. Their miRNA sponging activity formed a 65-node ceRNA network involving 15 miRNAs (e.g., miR-143–3p and miR-182–5p) and 47 mRNAs. Six targets (BRCA1, KRAS, MSH6, SMARCA4, SRC, and TSC1) exhibited significant correlations with immune infiltration (CD8⁺ T cells, Tregs, and MDSCs). High expression of BRCA1, KRAS, and MSH6 predicted poor survival, with protein-level upregulation confirmed in OCCC tissues.</div></div><div><h3>Conclusion</h3><div>This study delineates a circRNA-driven ceRNA network in OCCC, and identifies BRCA1, KRAS, and MSH6 as multi-omic biomarkers with immune-modulatory roles. These findings provide a basis for the development of RNA-targeted therapies against this ovarian cancer subtype.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"774 ","pages":"Article 110623"},"PeriodicalIF":3.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181906","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}