{"title":"Untargeted metabolomics and proteomics reveal the versatile effects of myeloperoxidase-oxidized LDL on endothelial cells.","authors":"Cecilia Tangeten, Axelle Bourez, Alexandre Rousseau, Virginie Imbault, Jianru Stahl-Zeng, Florence Souard, Xavier Bisteau, Cedric Delporte, Karim Zouaoui Boudjeltia, Pierre Van Antwerpen","doi":"10.1016/j.bbagen.2025.130865","DOIUrl":"10.1016/j.bbagen.2025.130865","url":null,"abstract":"<p><strong>Background: </strong>Myeloperoxidase-oxidized LDLs (Mox-LDLs) trigger endothelial cells and contribute to the development of atherosclerosis. However, the mechanisms underlying Mox-LDL-induced stimulation remain elusive. In this study, we applied untargeted metabolomics and proteomics approaches to investigate human umbilical vein endothelial cells (HUVECs) following exposure to Mox-LDLs.</p><p><strong>Methods: </strong>HUVECs were exposed for 24 h to Mox-LDLs (0 or 100 μg/ml) with or without native LDLs (0 or 1 mg/ml). Supernatants and cell lysates were analyzed by liquid chromatography coupled to mass spectrometry. Using Workflow4Metabolomics work environment, MZmine, SIRIUS and MetGem, we selected and identified key metabolites influenced by Mox-LDL treatment. For the proteomics analysis, we used DIA-NN and the FragPipe-Analyst application to detect proteins differentially expressed after Mox-LDL treatment.</p><p><strong>Results: </strong>Metabolomics analysis revealed increased levels of sphingolipids, phospholipids and oxidized-cholesterol derived compounds in HUVECs following Mox-LDL exposure. We also detected an increase in small peptides, likely reflecting Mox-LDLs catabolism. Mox-LDL treatment of HUVECs also altered the expression of proteins involved in hemostasis, cell adhesion, angiogenesis, inflammation and stress responses. In addition, proteins from the mitochondrial respiratory chain were upregulated after Mox-LDL treatment. Finally, a trihydroxy-unsaturated fatty acid was secreted by HUVECs exposed to Mox-LDLs and could serve as a biomarker of Mox-LDL exposure.</p><p><strong>Conclusions: </strong>Our findings suggest that Mox-LDLs are internalized and degraded by HUVECs. They seem to induce increased mitochondrial activity and oxidative stress, likely mediated by reactive oxygen species. We believe that HUVECs activate cytoprotective antioxidant coping mechanisms (glutathione synthesis, heme oxygenase-1…) to survive. Mox-LDLs may also modulate hemostasis and inflammatory responses.</p>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"130865"},"PeriodicalIF":2.2,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249494","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":"Seasonal and COVID-19 lockdown variations in PM<sub>2.5</sub> composition to apoptosis pathways and chemical toxicity in lung cells.","authors":"Ting-Hsuan Wu, Yu-Cheng Chen, Hong-Lin Chan, Hsiu-Chuan Chou","doi":"10.1016/j.bbagen.2025.130864","DOIUrl":"10.1016/j.bbagen.2025.130864","url":null,"abstract":"<p><strong>Objective: </strong>To investigate seasonal and COVID-19-lockdown variations in PM2.5 chemical composition in Taipei and the effects of those compositional differences on lung cell toxicity.</p><p><strong>Methods: </strong>PM2.5 was collected in warm (2021/07-2021/08) and cold (2021/11-2022/02) seasons and during LV2/LV3 COVID-19 alert periods. Composition (metals, PAHs) was analyzed and A549 and PC9 lung cells were exposed to equal mass concentrations (0-100 μg/mL) of extracted PM2.5. Cell viability, ROS, apoptosis, mitochondrial membrane potential and GSH/GPX4 were measured.</p><p><strong>Results: </strong>At equivalent mass concentrations (50 μg/mL), warm-season PM2.5 induced higher ROS and greater reduction in viability than cold-season PM2.5. LV2-period PM2.5 contained higher metal content and caused more severe cellular damage than LV3. Spearman correlation plus single-compound assays identified cadmium and Dibenzo[a,e]pyrene as components strongly associated with cytotoxicity.</p><p><strong>Conclusions: </strong>Seasonal and human-activity driven compositional changes-rather than mass concentration alone-affect PM2.5 toxicity in vitro; these results underscore the importance of controlling specific chemical emissions.</p>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"130864"},"PeriodicalIF":2.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237919","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":"Midkine and TNFSF10 as downstream molecules of type I interferon are involved in the treatment of myelofibrosis.","authors":"Yaoyao Chen, Fanxiang Yin, Xiaoqian Wang, Huilin Zhang, Ping Tang, Mengjiao Xue, Nannan Sun, Jin Li, Chang Chen, Bingjie Wang, Qingxuan Xin, Juanxia Zhou, Yingmei Li, Shuya Wang, Shaohua Yan, Jiani Li, Yunling Zhu, Bo Qin, Baohong Yue, Yong Jiang, Rongqun Guo","doi":"10.1016/j.bbagen.2025.130863","DOIUrl":"10.1016/j.bbagen.2025.130863","url":null,"abstract":"<p><p>Myelofibrosis (MF), a myeloproliferative neoplasm, remains incurable for most patients. Although some individuals are eligible for allogeneic hematopoietic stem cell transplantation, current therapies generally slow disease progression rather than achieve a cure. In this study, we found that type I interferon (IFN) treatment enhances midkine (MDK) expression, and MDK is involved in the differentiation and maturation of progenitor cells. Notably, MDK treatment drives tumor cells into the cell cycle, thereby increasing the therapeutic effect of busulfan. Furthermore, MDK promotes osteogenic differentiation of mesenchymal stem cells (MSC), contributing to the remodeling of the bone marrow microenvironment. In addition, type I IFN upregulates TNFSF10, leading to tumor cell death through mutual killing.</p>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"130863"},"PeriodicalIF":2.2,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205518","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}
Ricardo Esquivel-Garcia, Jorge Bravo-Martinez, Karina Bermeo, Isabel Arenas, David E. Garcia
{"title":"AMPK regulates BK-channel current in CA1 hippocampal neurons","authors":"Ricardo Esquivel-Garcia, Jorge Bravo-Martinez, Karina Bermeo, Isabel Arenas, David E. Garcia","doi":"10.1016/j.bbagen.2025.130862","DOIUrl":"10.1016/j.bbagen.2025.130862","url":null,"abstract":"<div><div>AMP-activated protein kinase (AMPK) is a fundamental energy sensor fine-tuning cellular activity based on ATP availability. On the other hand, BK-channel current is tightly regulated by leptin, which in turn regulates neuronal excitability by modulating ion channels such as the BK-channel. However, this mechanism remains unclear to date. In this work we aimed to determine whether AMPK mediates the leptin regulation on BK-channel. We hypothesized that leptin regulation of BK-channel through AMPK underlies the modulating changes in neuronal excitability of CA1 hippocampal neurons. By using patch-clamping methods on CA1 pyramidal neurons in brain slices and biochemical reagents, we found that AMPK activation with AICAR inhibits BK-channel current, while AMPK inhibition with Compound C enhances BK-channel activity. Remarkably, AMPK activation reverses BK-channel current enhanced by leptin supporting an AMPK-dependent metabolic regulation of BK. Accordingly, current-clamp experiments revealed that AMPK manipulations significantly affect leptin responses on CA1 neuronal firing. These results support AMPK as a key mediator of the interplay between leptin and neuronal excitability, readily integrating metabolic signals with the computing state of firing outputs in CA1 hippocampal neurons.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130862"},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136334","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}
Magdalena Szpunar , David Aebisher , Bogumił Cieniek , Ireneusz Stefaniuk , Łukasz Dubiel , Andrzej Wal
{"title":"Evidence for singlet oxygen production from indocyanine green by electron paramagnetic resonance","authors":"Magdalena Szpunar , David Aebisher , Bogumił Cieniek , Ireneusz Stefaniuk , Łukasz Dubiel , Andrzej Wal","doi":"10.1016/j.bbagen.2025.130861","DOIUrl":"10.1016/j.bbagen.2025.130861","url":null,"abstract":"<div><div>Indocyanine green (ICG) is a well-known dye used for cardiovascular fluorescence imaging in medicine and a potential photosensitizer for photodynamic therapy. Using electron paramagnetic resonance (EPR), we have shown that illumination of aqueous solutions of ICG leads to the generation of singlet oxygen. The use of a selective spin trap allowed for the rate of singlet oxygen generation to be determined which provides evidence that ICG undergoes Type II photosensitization.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130861"},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The F54L mutation of Thioredoxin shows protein instability and increased fluctuations of the catalytic center","authors":"Takumi Baba , Go Ueno , Chika Ohe , Shuku Saji , Sachiko Yamamoto , Masaki Yamamoto , Hiroshi Nakagawa , Nobuo Okazaki , Mamoru Ouchida , Iori Kawasaki Ohmori , Kohei Takeshita","doi":"10.1016/j.bbagen.2025.130860","DOIUrl":"10.1016/j.bbagen.2025.130860","url":null,"abstract":"<div><div>Thioredoxin is a ubiquitous redox protein that acts as an electron donor via its conserved dithiol motif (C32GPC35), catalyzing dithiol–disulfide exchange to regulate the redox state of target proteins. It supports antioxidant defense via peroxiredoxins, facilitates DNA synthesis by donating electrons to ribonucleotide reductase, and regulates redox-sensitive signaling pathways, including those controlling transcription and apoptosis. Neuronal degeneration and chronic kidney disease have been observed in <em>Txn</em>-F54L mutant rats; however, the details of why the <em>Txn</em> mutation causes these phenomena remain unknown. The present study aimed to elucidate the functional and structural changes caused by the F54L mutation. The Thioredoxin-F54L showed less insulin-reducing activity and more thermosensitivity to denaturation in the body temperature range compared to the wild type. The crystal structure revealed that F54 forms hydrophobic interactions with the surrounding hydrophobic amino acids. In addition, molecular dynamics simulation predicts increased fluctuations around the F54L mutation and a tendency for the distance between residues C32 and C35 at the catalytic center to be widened. The increased distance between residues C32 and C35 of the catalytic center may affect the reducing activity of the enzyme on the substrate. The finding that Thioredoxin-F54L is prone to denaturation at normal body temperature may reduce the normally functioning Thioredoxin. These molecular characteristics of Thioredoxin-F54L may be related to brain and kidney disease development in the <em>Txn</em>-F54L rats.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130860"},"PeriodicalIF":2.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069073","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}
Luiz Saramago , Nallely Cabrera , Beatriz Aguirre , Helga Gomes , Bruno Moraes , Valdir Braz , Itabajara da Silva Vaz Jr. , Mayra A. Marques , Jerson L. Silva , Tomohiro Okagawa , Satoru Konnai , Ruy Pérez-Montfort , Carlos Logullo , Jorge Moraes
{"title":"Rhipicephalus microplus triosephosphate isomerase dimer interface is stabilized by a key cysteine residue","authors":"Luiz Saramago , Nallely Cabrera , Beatriz Aguirre , Helga Gomes , Bruno Moraes , Valdir Braz , Itabajara da Silva Vaz Jr. , Mayra A. Marques , Jerson L. Silva , Tomohiro Okagawa , Satoru Konnai , Ruy Pérez-Montfort , Carlos Logullo , Jorge Moraes","doi":"10.1016/j.bbagen.2025.130857","DOIUrl":"10.1016/j.bbagen.2025.130857","url":null,"abstract":"<div><div>The functional significance of a non-conserved cysteine residue (C86) proximal to the interfacial region of <em>Rhipicephalus microplus</em> triosephosphate isomerase (RmTIM) was investigated through systematic substitution with aspartic acid (C86D), lysine (C86K), and alanine (C86A) via site-directed mutagenesis. Kinetic analyses revealed substantial perturbations in enzymatic parameters for the C86D and C86K variants, with marked alterations in maximal velocity (<em>V</em><sub>max</sub>), substrate affinity (<em>K</em><sub>m</sub>), catalytic turnover (<em>k</em><sub>cat</sub>), and catalytic efficiency (<em>k</em><sub>cat</sub>/<em>K</em><sub>m</sub>). Thermodynamic destabilization was universally observed across all mutants via Protein Thermal Shift assays, with reductions in melting temperature (<em>T</em><sub>m</sub>) ranging from 15.7 to 27.1 °C relative to the wild-type enzyme (Wt-TIM). Chemical denaturation studies employing guanidine hydrochloride demonstrated heightened susceptibility to unfolding in all mutants, with destabilization profiles following the order: C86K > C86D > C86A. Computational structural analyses elucidated molecular mechanisms underlying these perturbations. Disruption of a putative salt bridge between residues D49 and K18 was predicted in the C86K mutant, potentially destabilizing the dimeric interface. Comparative free energy calculations (ΔG) further corroborated these findings: Wt-TIM exhibited a ΔG of −21.2 kcal/mol and an interfacial contact area of 1604.8 Å<sup>2</sup>, indicative of robust dimeric stabilization. In contrast, the C86K mutant displayed diminished stability (ΔG = −16.0 kcal/mol) despite an expanded interface (1615.6 Å<sup>2</sup>), suggesting compromised packing efficiency. These observations imply that C86, while not directly conserved, plays a critical structural role in maintaining interfacial integrity and catalytic competence. The pronounced destabilization and kinetic impairment observed in the C86K variant highlight the residue's significance in RmTIM functionality. This residue-specific destabilization strategy may aid in the rational design of acaricidal compounds targeting interfacial regions of RmTIM, taking advantage of structural vulnerabilities produced by non-conserved residues.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130857"},"PeriodicalIF":2.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063432","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":"Circ-ATF7IP promotes IL13RA1 dependent M2 polarization of macrophage via sponging MiR-488-3p in papillary thyroid carcinoma","authors":"Yan Hu , Shujun Xia , Yanhua Yang , Weiwei Zhan","doi":"10.1016/j.bbagen.2025.130855","DOIUrl":"10.1016/j.bbagen.2025.130855","url":null,"abstract":"<div><div>The preoperative assessment of lymph node metastasis (LNM) is of critical importance for the selection of appropriate surgical and therapeutic strategies for papillary thyroid carcinoma (PTC). However, the mechanisms underlying LNM in PTC remain unclear, and effective diagnostic tools are currently lacking. This study aims to identify circRNAs as diagnostic molecular markers for LNM and to investigate their molecular mechanisms in the occurrence of LNM in PTC. In this study, bioinformatics analysis and qPCR verification were used and identified that circ-ATF7IP was the key molecule in PTC progression and overexpressed in PTC patients with LNM. Mechanistically, circ-ATF7IP acts as a molecular sponge for miR-488-3p in PTC cells. PTC cell-derived miR-488-3p acts on macrophage (Mɸ) through exosome transfer. In Mɸ, miR-488-3p negatively regulates IL13RA1 at post transcription stage, facilitating M2 phenotype polarization. This reshapes the tumor microenvironment, enhancing tumor invasiveness. To be brief, circ-ATF7IP is a newly identified biomarker for PTC related LNM. Targeting circ-ATF7IP/miR-488-3p/IL13RA1 axis is a promising therapeutic strategy for PTC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130855"},"PeriodicalIF":2.2,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057444","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":"Rapid kinase activity detection and kinetic analysis using a convenient EGFR FRET-based detection probe","authors":"Kittitat Jaengwang , Suleeporn Pommayon , Chanikan Sonklin , Kiattawee Choowongkomon , Dujdaun Waraho-Zhmayev , Lueacha Tabtimmai","doi":"10.1016/j.bbagen.2025.130854","DOIUrl":"10.1016/j.bbagen.2025.130854","url":null,"abstract":"<div><div>In modern drug discovery, there is a pressing need for rapid, cost-effective, and accessible methods to evaluate the biological activities of newly synthesized compounds. Traditional kinase assay platforms are often labor-intensive, time-consuming, and require specialized equipment or expertise. To address these limitations, we developed and validated a convenient in vitro kinase assay based on a recombinant biosensor, Picchu-B, constructed using a bacterial expression system. Picchu-B, derived from the live-cell EGFR FRET biosensor Picchu, was successfully expressed as a highly soluble, fluorescent protein. It served as a direct Probe for EGFR kinase, enabling real-time FRET-based detection of kinase activity. Optimization of Picchu-B concentration revealed a linear correlation between FRET signal intensity and EGFR-TK levels. The biosensor demonstrated high selectivity for EGFR and its clinically relevant mutants (e.g., T790M/L858R), with minimal cross-reactivity to unrelated kinases such as JAK-2. Enzyme kinetic studies confirmed nucleotide specificity of EGFR-TK in the presence of Picchu-B. This study highlights Picchu-B as a practical and scalable tool for EGFR-targeted drug screening, offering significant advantages in speed, and simplicity over conventional approaches.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130854"},"PeriodicalIF":2.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032448","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}
Songbo Yang , Xianghuai Long , Wuliang Diao , Jiaxing Yang , Anyuan Jiang , Hongfei Wu
{"title":"m1A methylation-mediated upregulation of RILsPL1 promotes colorectal cancer progression via the CaMKII/CREB signaling pathway","authors":"Songbo Yang , Xianghuai Long , Wuliang Diao , Jiaxing Yang , Anyuan Jiang , Hongfei Wu","doi":"10.1016/j.bbagen.2025.130856","DOIUrl":"10.1016/j.bbagen.2025.130856","url":null,"abstract":"<div><div>Colorectal cancer (CRC) remains one of the most lethal malignancies globally, driven by complex molecular mechanisms that contribute to its progression and metastasis. This study focuses on the role of N1-methyladenosine (m<sup>1</sup>A) RNA methylation in CRC, particularly its effect on Rab Interacting Lysosomal Protein-Like 1 (RILPL1) expression and the downstream activation of the CaMKII/CREB signaling pathway. Bioinformatics analysis identified RILPL1 as a key gene associated with poor CRC prognosis, exhibiting increased expression levels in cancerous tissues, with further elevation in metastatic samples. Functional assays demonstrated that m<sup>1</sup>A methylation enhances the stability of RILPL1 mRNA, a process dynamically regulated by the opposing actions of the demethylase ALKBH1 and the methyltransferase TRMT6. Loss-of-function and gain-of-function studies showed that RILPL1 promotes CRC cell viability, invasion, and migration, highlighting its oncogenic role. <em>In vivo</em>, RILPL1 knockdown markedly suppressed tumor growth in a nude mouse xenograft model. Furthermore, the CaMKII/CREB signaling pathway was identified as a critical mediator, with RILPL1 expression levels directly correlating with the phosphorylation of CaMKII and CREB both <em>in vitro</em> and <em>in vivo</em> xenograft models. Pharmacological rescue experiments confirmed this dependency, as a CaMKII activator reversed the effects of RILPL1 knockdown, while a specific inhibitor blocked this rescue. These findings suggest that dynamic m<sup>1</sup>A methylation-driven upregulation of RILPL1 contributes to CRC progression through the activation of the CaMKII/CREB signaling pathway, offering potential therapeutic targets for CRC treatment.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 12","pages":"Article 130856"},"PeriodicalIF":2.2,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013811","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}