Archives of biochemistry and biophysics最新文献

{"title":"EGFR and IRE1α pathways are associated with distinct immunomodulatory gene expression profiles in NSCLC cells with acquired resistance to EGFR TKIs","authors":"Yi-Shiuan Wang ,&nbsp;Hsiu-Chuan Chou ,&nbsp;En-Chi Liao ,&nbsp;Hsin-Yi Chen ,&nbsp;Meng-Wei Lin ,&nbsp;Yu-Shan Wei ,&nbsp;Li‐Hsun Lin ,&nbsp;Yi-Ru Chang ,&nbsp;Han Meng ,&nbsp;Yueh-Feng Wen ,&nbsp;Hong-Lin Chan","doi":"10.1016/j.abb.2026.110762","DOIUrl":"10.1016/j.abb.2026.110762","url":null,"abstract":"<div><div>EGFR-TKI-resistant cell lines were established by long-term exposure to gefitinib, afatinib, and osimertinib via the PC9 model. This model helps study EGFR-TKI resistance mechanisms in non-small cell lung cancer (NSCLC) and may offer insights to improve treatment outcomes, particularly for patients unresponsive to anti-PD-1/PD-L1 therapies. We investigated molecular alterations in these resistant cell lines using multi-omics techniques, including genome sequencing, proteomics, and transcriptomics.</div><div>Differential dependencies on EGFR downstream pathways were observed among resistant cell lines. Immune evasion mechanisms were analyzed to identify alterations in EGFR downstream pathways and unfolded protein response (UPR) elements contributing to immune-related transcriptional patterns. Afatinib-resistant cells exhibited the most pronounced immunosuppressive-like transcriptional features compared to gefitinib- and osimertinib-resistant cells. This was characterized by elevated PD-L1 expression, minimal changes in MHC class 1 levels, down-regulation of shared immune-modulated gene sets, and a cytokine profile favoring immunosuppression (e.g., lower IL-6, CXCL10, IFN-γ, CCL22; higher IL-8). These findings suggest a poor prognosis and limited efficacy of anti-PD-1/PD-L1 immunotherapy in NSCLC patients with similar resistance profiles. Notably, inhibition of IRE1α signaling partially reversed this immunosuppressive-like transcriptional signature, indicating a potential strategy to restore immune responsiveness in afatinib-resistant NSCLC. Our study underscores the distinct remodeling effects of different EGFR-TKIs on tumor-cell–intrinsic immunoregulatory pathways. Targeting endoplasmic reticulum (ER) stress pathways alongside immune checkpoint inhibitors may be crucial for overcoming resistance mechanisms identified here. These insights provide a rationale for personalized treatment strategies tailored to the immune-related gene-expression profiles observed in EGFR-TKI–resistant NSCLC models, aiming to enhance therapeutic responses and improve clinical outcomes.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"779 ","pages":"Article 110762"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163819","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":"Echinoderm collagen as a neuromodulatory antioxidant: biochemical characterization and molecular interaction with NMDA receptor","authors":"Rozirwan ,&nbsp;Yoga Winarta ,&nbsp;Isnaini ,&nbsp;Wike Ayu Eka Putri ,&nbsp;Fauziyah ,&nbsp;Riris Aryawati ,&nbsp;Nadila Nur Khotimah ,&nbsp;Melki ,&nbsp;Redho Yoga Nugroho ,&nbsp;Chaidir","doi":"10.1016/j.abb.2026.110758","DOIUrl":"10.1016/j.abb.2026.110758","url":null,"abstract":"<div><div>Marine collagen is increasingly recognized as a sustainable biomaterial for therapeutic applications; however, collagen derived from tropical Echinodermata remains underexplored, particularly in the context of neuropharmacology. This study investigated the biochemical characteristics, antioxidant activity, and neuromodulatory potential of collagen isolated from three tropical echinoderm species, <em>Holothuria atra</em>, <em>Acanthaster planci</em>, and <em>Culcita novaeguineae</em>, collected from the neritic zone of Pahawang Island, Indonesia. The isolated collagens exhibited very strong antioxidant activity, with IC₅₀ values of 4.43 (<em>C. novaeguineae</em>), 10.84 (<em>H. atra</em>), and 21.78 μg/mL (<em>A. planci</em>), surpassing several previously reported marine collagen sources. Structural characterization using Liquid Chromatography-Mass Spectrometry (LC-MS), Fourier Transform Infrared Spectroscopy (FTIR), and Carbon-13 Nuclear Magnetic Resonance (¹³C NMR) revealed glutamic acid, proline, glycine, and valine as dominant amino acid residues, supporting the stability and functional integrity of the collagen matrix. Furthermore, <em>in silico</em> molecular docking analysis demonstrated a favorable interaction between glutamic acid and the N-Methyl-<span>d</span>-Aspartate (NMDA) receptor GluN1a/GluN2B (PDB ID: <span><span>4PE5</span><svg><path></path></svg></span>), with a binding affinity of ΔG = −5.25 kcal/mol and an inhibition constant (Ki) of 142.02 μM, indicating a potential neuromodulatory mechanism. By integrating biochemical characterization with molecular interaction analysis, this study provides the first evidence that collagen from tropical echinoderms exhibits dual antioxidant and neuromodulatory potential, highlighting its promise as a sustainable marine-derived biomaterial for neurodegenerative disease-related drug discovery.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"779 ","pages":"Article 110758"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154185","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 an N-methylpyrazole derivative as a selective inhibitor of breast cancer resistance protein (BCRP/ABCG2)","authors":"Andrezza Braiane Ferreira Siridó ,&nbsp;Arthur Henrique Gomes de Oliveira ,&nbsp;Julia Poletto ,&nbsp;Thales Kronenberger ,&nbsp;Fabiane Gomes de Moraes Rego ,&nbsp;Geraldo Picheth ,&nbsp;Marc Le Borgne ,&nbsp;Ahcène Boumendjel ,&nbsp;Fernanda Andreia Rosa ,&nbsp;Glaucio Valdameri ,&nbsp;Vivian Rotuno Moure","doi":"10.1016/j.abb.2026.110761","DOIUrl":"10.1016/j.abb.2026.110761","url":null,"abstract":"<div><div>Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters remains a major obstacle to cancer chemotherapy, particularly at later disease stages with metastases. Among the 48 human ABC proteins, P-glycoprotein (P-gp/ABCB1), multidrug resistance-associated protein 1 (MRP1/ABCC1), and breast cancer resistance protein (BCRP/ABCG2) are the most studied ABC transporters associated with MDR. Inhibition of ABC transporters has been considered as one possible strategy to overcome MDR. In this study, twelve N-methylpyrazole derivatives were evaluated as inhibitors of ABCB1, ABCC1, and ABCG2. Several compounds selectively inhibited ABCG2 while showing no activity against ABCB1 or ABCC1. The most potent derivative, <strong>1l</strong>, inhibited more than 50% of ABCG2 activity at 10 μM and displayed substrate-independent inhibition, with IC₅₀ values ranging from 1.6 to 3.8 μM depending on the fluorescent probe used. Compound <strong>1l</strong> exhibited only mild cytotoxicity and was not transported itself by ABCG2. Mechanistic studies revealed that <strong>1l</strong> induced conformational changes in ABCG2, as evidenced by increased binding of the 5D3 conformational antibody. Combination assays with established ABCG2 inhibitors, including chromone <strong>4a</strong> and indeno-[1,2-<em>b</em>]indole <strong>5e</strong>, showed neither synergistic nor antagonistic effects. Induced-fit docking simulations supported the experimental data, indicating that <strong>1l</strong> binds within the central transmembrane cavity of ABCG2, engaging key residues such as Phe439 and stabilizing inward-facing conformations. Finally, co-treatment with <strong>1l</strong> restored sensitivity of ABCG2-overexpressing cells to the anticancer drug SN38, effectively reversing the MDR phenotype. Collectively, these results identify N-methylpyrazole derivatives as promising selective inhibitors of ABCG2.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"779 ","pages":"Article 110761"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146154184","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":"ETS1 targets the SENP2/HSPA8/FUNDC1 axis to ameliorate bronchopulmonary dysplasia by inhibiting mitochondrial damage-induced autophagy.","authors":"Min Yang, Qinglan Yang, Yanni Meng, Jiyan Zhang, Shuangjie Li","doi":"10.1016/j.abb.2026.110839","DOIUrl":"https://doi.org/10.1016/j.abb.2026.110839","url":null,"abstract":"<p><p>Mitochondrial damage and subsequent aberrant mitophagy are critical drivers of alveolar simplification in bronchopulmonary dysplasia (BPD). E26 transformation specific-1 (ETS1) is a transcription factor whose role in BPD and its regulation of mitophagy have not been fully investigated. This study aims to explore the role of ETS1 in mitophagy in BPD and its underlying molecular mechanisms. Using hyperoxia-induced BPD models in cells and mice, we found that ETS1 overexpression simplified alveolar structure, reduced alveolar number, inhibited mitophagy, improved cell viability and mitochondrial damage. Mechanistically, EST1 promoted the transcription of SENP2. After SENP2 removed the SUMO1 modification from FUNDC1, the binding site of HSPA8 was exposed, thereby promoting the degradation of FUNDC1. In BPD mice, ETS1 overexpression alleviated lung injury and inhibited mitophagy, while SENP2 knockdown reversed these effects. In conclusion, ETS1, as a novel transcriptional hub, maintained mitochondrial homeostasis by coordinating the deSUMOylation-coupled FUNDC1 degradation pathway. ETS1 blocked mitochondrial damage-induced mitophagy by targeting the SENP2/HSPA8/FUNDC1 axis, providing a promising strategy for the treatment of BPD.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110839"},"PeriodicalIF":3.0,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810012","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":"Inhibition of cytochrome P450 enzymes by cirsimaritin and its properties in vitro.","authors":"Xiangcheng Li, Yawei Shi, Dandan Liu","doi":"10.1016/j.abb.2026.110834","DOIUrl":"https://doi.org/10.1016/j.abb.2026.110834","url":null,"abstract":"<p><strong>Background: </strong>The flavonoid cirsimaritin has pharmacological activities that potentially in modulate inflammatory responses, tumor progression, and glucolipid metabolism. However, its influence on cytochrome P450 (P450) enzyme activity remains unexplored.</p><p><strong>Objective: </strong>This study examines the influence of cirsimaritin on P450 activity, aiming to offer further guidance for its clinical use.</p><p><strong>Methods: </strong>The effect of cirsimaritin on key P450 isoform activities was investigated in pooled human liver microsomes (HLMs) using specific substrates. The half-maximal inhibitory concentrations (IC₅₀) for the inhibition of P450 isoforms were determined using different doses of cirsimaritin. The type of inhibition was further assessed using different concentrations of substrates. Furthermore, time-dependent experiments were performed to obtain the corresponding kinetic parameters.</p><p><strong>Results: </strong>Cirsimaritin inhibited the activity of CYP1A2, CYP3A4, and CYP2C9 with significant concentration-dependent changes, and the IC₅₀ values were 18.4 ± 2.7, 15.3 ± 2.6, and 9.67 ± 1.9 μM, respectively. Cirsimaritin exhibited non-competitive inhibition of CYP3A4, with the inhibition constant (K_i) value of 7.81 ± 0.79 μM. Cirsimaritin was a competitive inhibitor of CYP1A2 and CYP2C9, with K_i values of 9.33 ± 0.65 μM and 4.81 ± 0.51 μM, respectively. In addition, the inhibitory effect of cirsimaritin on CYP3A4 was further found to be time-dependent, with the maximal rate of enzyme inactivation (k_inact) value of 0.035 ± 0.005 min^-1 and the concentration of cirsimaritin at half of the k_inact (K_I) value of 6.52 ± 0.81 μM.</p><p><strong>Conclusions: </strong>The observed inhibition of CYP1A2, CYP3A4, and CYP2C9 by cirsimaritin indicates its potential to cause herb-drug interactions with drugs metabolized by these isoforms. Further in vivo studies are needed to confirm such interactions.</p>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":" ","pages":"110834"},"PeriodicalIF":3.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809976","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":"Exosomes derived from HISLA overexpressed-adipose stem cells accelerate wound healing in diabetic foot ulcers by regulating HIF-1α signal transduction","authors":"Wei Zhao ,&nbsp;Haili Zhang ,&nbsp;Shujun Liu ,&nbsp;Yahui Cao ,&nbsp;Caisheng Wang ,&nbsp;Yanfei Wang","doi":"10.1016/j.abb.2026.110747","DOIUrl":"10.1016/j.abb.2026.110747","url":null,"abstract":"<div><div>Diabetic foot ulcers (DFUs), characterized by impaired angiogenesis and a chronic inflammatory milieu, represent a severe complication of diabetes. This study investigates the therapeutic potential of exosomes derived from HISLA-overexpressing adipose-derived stem cells (HISLA-ex) in enhancing DFU healing. <em>In vitro</em>, under high glucose conditions, HISLA-ex significantly elevated HISLA expression by approximately 3-fold in endothelial cells, markedly improving cell viability at 24–72 h in HMEC-1 cells, reducing pro-inflammatory cytokines IL-1 and IL-6, and enhancing tube formation capacity as evidenced by increased branching points and total tube length. Subsequently, a DFU rat model was established by inducing diabetes with streptozotocin followed by creation of a full-thickness cutaneous wound on the foot dorsum. HISLA-ex application substantially accelerated wound closure and modulated key angiogenic factors: upregulating VEGFA and Ang-1 while suppressing TSP-1. Furthermore, HISLA-ex shifted the helper T (Th)1/Th2 balance by inhibiting T-bet and pro-inflammatory cytokines (IFN-γ and TNF-α) and promoting GATA3 and anti-inflammatory cytokines (IL-4 and IL-13) <em>in vivo</em> and <em>in vitro</em>. Mechanistically, these effects were mediated through activation of the HIF-1α pathway, confirmed by both gain- and loss-of-function experiments, and abolished upon HIF-1α inhibition. Collectively, our results demonstrate that HISLA-ex synchronously promotes angiogenesis and corrects Th immune dysfunction, offering a novel RNA-based exosomal therapeutic strategy for the treatment of DFUs.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"778 ","pages":"Article 110747"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045943","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":"BHMT Prevents renal ischemia/reperfusion injury via suppressing ROS-induced apoptosis by targeting NOX4","authors":"Chong Sun ,&nbsp;Hao Hu ,&nbsp;Xinwei Yuan ,&nbsp;Xingyu Chen ,&nbsp;Fang Fang ,&nbsp;Yunlong Liu ,&nbsp;Zhijun Chen ,&nbsp;Han Guan","doi":"10.1016/j.abb.2026.110745","DOIUrl":"10.1016/j.abb.2026.110745","url":null,"abstract":"<div><h3>Background</h3><div>Ischemia/reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), primarily driven by the increased production of reactive oxygen species (ROS). Elevated ROS levels can lead to cell apoptosis. However, effective therapeutic targets for IRI remain limited.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the potential mechanisms by which BHMT modulates IRI.</div></div><div><h3>Methods</h3><div>RT-qPCR and Western blot were used to assess RNA and protein expression levels. MTT assay, flow cytometry, and ROS-related assays were employed to evaluate renal cell injury <em>in vitro</em>. Mechanistic studies were conducted to explore molecular interactions, while <em>in vivo</em> assays were used to assess IRI.</div></div><div><h3>Results</h3><div>Betaine-homocysteine S-methyltransferase (BHMT) was found to be downregulated in both ischemia/reperfusion (I/R) and hypoxia/reoxygenation (H/R) models. BHMT overexpression mitigated the effects of H/R or I/R on ROS production and cell apoptosis. Mechanistically, BHMT enhanced the synthesis of S-adenosylmethionine (SAM), which in turn increased DNA-methyltransferase (DNMT) activity. This facilitated methylation of the NADPH Oxidase 4 (NOX4) promoter, suppressing NOX4 transcription and expression. Rescue assays confirmed that BHMT reduced ROS production and cell apoptosis in H/R-treated renal cells by downregulating NOX4. Furthermore, elevated expression of Samd4a in I/R accelerated renal fibrosis progression through activation of the Wnt/β-catenin signaling pathway.</div></div><div><h3>Conclusion</h3><div>BHMT reduces ROS-induced apoptosis by downregulating NOX4, offering protection against renal IRI. Additionally, targeting Samd4a expression may provide a therapeutic approach for preventing chronic kidney disease in kidney injury models.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"778 ","pages":"Article 110745"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146123378","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":"New insight into the self-association of human apolipoprotein A-I","authors":"Bryan Y. Kang ,&nbsp;Juliette M. Warner ,&nbsp;Paul M.M. Weers","doi":"10.1016/j.abb.2026.110731","DOIUrl":"10.1016/j.abb.2026.110731","url":null,"abstract":"<div><div>Apolipoprotein A-I (apoA-I) is a critical plasma protein responsible for high-density lipoprotein formation, playing a vital role in reverse-cholesterol transport. Lipid-free apoA-I has two domains, an N-terminal helix bundle and a structurally less organized C-terminal (CT) region. In solution, apoA-I self-associates, which is mediated by the CT domain. To gain insight into the self-associated state, cysteine was introduced in each of the three putative α-helices of the CT domain: S201C for helix-8, Q216C for helix-9, and S231C for helix-10, and a S25C mutation served as a control. The single cysteine mutants were covalently labeled with pyrene, a spatially sensitive probe producing fluorescence excimers when in close proximity. At a protein concentration of 0.2 mg/mL, strong excimers were observed for S201C-pyrene-labeled apoA-I, while excimer intensity was weaker for Q216C- and S231C-pyrene-labeled apoA-I. When the protein was diluted 10-fold, pyrene excimer fluorescence was reduced, but excimer fluorescence remained strong for S201C-apoA-I, implying the protein remained in a self-associated state. Cysteine-specific crosslinking was more efficient for S201C compared to Q216C and S231C apoA-I mutants, in agreement with the pyrene excimer analysis. Size-exclusion chromatography demonstrated that at 0.02 mg/mL, apoA-I is present as a mixture of monomers and dimers, and therefore the observed pyrene excimers at 0.02 mg/mL are caused by dimerization of apoA-I. In the apoA-I dimer, helix-8 is more buried and positioned near a neighboring helix-8, while helices-9 and -10 are further apart and more exposed. This structural arrangement potentially results in an optimal position for helix-10 to engage in lipid binding.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"778 ","pages":"Article 110731"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931877","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":"Influence of HIF1A-AS2 and miR-590-3p on trophoblast function and inflammation control in HTR-8/SVneo trophoblast cells","authors":"Peiqu Zhong ,&nbsp;Xiaoping Jia ,&nbsp;Qiongfang Chen ,&nbsp;Fengmei Tang ,&nbsp;Wanying Liang ,&nbsp;Youcai Liang ,&nbsp;Jiayuan Zhang ,&nbsp;Lijian Zhao","doi":"10.1016/j.abb.2026.110738","DOIUrl":"10.1016/j.abb.2026.110738","url":null,"abstract":"<div><div>Hypoxia-inducible factor 1 alpha antisense RNA 2 (HIF1A-AS2) and microRNA-590-3p (miR-590-3p) have been linked to inflammation and preeclampsia. In HTR-8/SVneo cells, HIF1A-AS2 was overexpressed and miR-590-3p mimic was introduced, and proliferation, migration/invasion and apoptosis were assessed by proliferation assays, wound-healing and Matrigel invasion assays, and flow cytometry, while molecular alterations were analyzed by quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence. HIF1A-AS2 overexpression enhanced proliferation and motility and reduced apoptosis, increased insulin-like growth factor 2 messenger RNA-binding protein 1 (IGF2BP1), and decreased NLR family pyrin domain containing 3 (NLRP3), gasdermin D (GSDMD) and cleaved caspase-1. Conversely, miR-590-3p suppressed IGF2BP1 and partially reversed HIF1A-AS2-associated phenotypes. Together, these data defined a HIF1A-AS2–miR-590-3p–IGF2BP1 axis linking trophoblast behaviour to inflammatory effector signalling.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"778 ","pages":"Article 110738"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028318","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":"LncRNA KCNQ1OT1 modulates M2 macrophage polarization and angiogenic signaling via the miR-142-3p/TRIM24 axis in retinal neovascularization","authors":"Chunhong Yu ,&nbsp;Weiwei Xiong ,&nbsp;Yuezhi Zhang ,&nbsp;Hongwei Lu ,&nbsp;Liwen Xu ,&nbsp;Zijing Ouyang","doi":"10.1016/j.abb.2026.110750","DOIUrl":"10.1016/j.abb.2026.110750","url":null,"abstract":"<div><h3>Background</h3><div>Retinopathy of prematurity (ROP) is a major cause of childhood blindness, driven by hypoxia-induced VEGF overproduction. Anti-VEGF therapy has limitations including recurrence and potential side effects, highlighting the need for upstream interventions. M2 macrophages contribute to ROP pathogenesis, but the regulatory mechanisms controlling their polarization remain unclear.</div></div><div><h3>Methods</h3><div>We explored the regulatory interplay among lncRNA KCNQ1OT1, miR-142-3p, and TRIM24 in RAW264.7 and THP-1 macrophages, human retinal microvascular endothelial cells (HRMECs), and an oxygen-induced retinopathy (OIR) mouse model. Interactions were validated via dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays. Effects on macrophage polarization and endothelial function were assessed using flow cytometry, immunofluorescence, and proliferation, migration, and tube formation assays. OIR mice received AAV-mediated KCNQ1OT1 delivery, followed by retinal histology, immunostaining, cytokine measurements, TUNEL assays, RT-qPCR, and Western blot analyses.</div></div><div><h3>Results</h3><div>KCNQ1OT1 acted as a competitive endogenous RNA to sequester miR-142-3p, partially relieving suppression of TRIM24 and attenuating STAT6-mediated M2 polarization. In macrophages, KCNQ1OT1 overexpression reduced M2 markers and VEGFA expression, diminishing pro-angiogenic effects on HRMECs. In OIR mice, AAV-KCNQ1OT1 delivery was associated with reduced retinal neovascularization, decreased M2 macrophage infiltration, and lower VEGFA and inflammatory cytokine levels.</div></div><div><h3>Conclusions</h3><div>The KCNQ1OT1/miR-142-3p/TRIM24 axis influences macrophage polarization and angiogenic signaling in ROP. While preliminary, these findings suggest that targeting this upstream regulatory network may complement existing VEGF-targeted therapies.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"778 ","pages":"Article 110750"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137063","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}