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LncRNA HOTAIR promotes aerobic glycolysis by recruiting Lin28 to induce inflammation and apoptosis in acute lung injury.
IF 3.6 3区 生物学
RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-03-07 DOI: 10.1080/15476286.2025.2475255
Junjie Xie, Zhicong Zheng, Bin Wang, Jianfang Zhang, Junqi Jiang, Fengde Wu, Xiangming Zhong, Jianfeng Chen
{"title":"LncRNA HOTAIR promotes aerobic glycolysis by recruiting Lin28 to induce inflammation and apoptosis in acute lung injury.","authors":"Junjie Xie, Zhicong Zheng, Bin Wang, Jianfang Zhang, Junqi Jiang, Fengde Wu, Xiangming Zhong, Jianfeng Chen","doi":"10.1080/15476286.2025.2475255","DOIUrl":"10.1080/15476286.2025.2475255","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a life-threatening condition with high rates of morbidity and mortality. Recently, there has been growing evidence suggesting a link between lncRNA HOTAIR and ALI. Nonetheless, the precise role and mechanism of lncRNA HOTAIR in ALI remain to be fully elucidated. siHOTAIR transfection, qPCR detection (HOTAIR), ELISA (TNF-α, IL-6, and IL-1β), Lactate detection, Glucose uptake experiment, Cell Apoptosis Analysis, Fluorescence in situ hybridization (FISH) assay. Through siHOTAIR transfection, we discovered that HOTAIR plays a role in the secretion of inflammatory factors in ALI and further regulates glucose uptake and metabolism in lung epithelial cells. Moreover, a comparison between HOTAIR knockdown cells and HOTAIR overexpression cells revealed that HOTAIR promotes cellular aerobic sugar metabolism, leading to increased secretion of inflammatory factors and cell apoptosis. Our in-depth research also identified an interaction between HOTAIR and the LIN28 protein. Knocking down HOTAIR resulted in the downregulation of LIN28 protein expression, which subsequently inhibited the expression of the glucose transporter GLUT1. This indicates that HOTAIR facilitates glucose uptake and boosts cellular aerobic glycolysis by modulating the LIN28 protein, thereby promoting inflammation and apoptosis in acute lung injury. The research findings presented in this article offer significant insights into the function of HOTAIR in ALI and suggest a potential therapeutic target for the treatment of this condition.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Placental malaria induces a unique methylation profile associated with fetal growth restriction.
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-06 DOI: 10.1080/15592294.2025.2475276
Nida Ozarslan, Corina Mong, John Ategeka, Lin Li, Sirirak Buarpung, Joshua F Robinson, Jimmy Kizza, Abel Kakuru, Moses R Kamya, Grant Dorsey, Philip J Rosenthal, Stephanie L Gaw
{"title":"Placental malaria induces a unique methylation profile associated with fetal growth restriction.","authors":"Nida Ozarslan, Corina Mong, John Ategeka, Lin Li, Sirirak Buarpung, Joshua F Robinson, Jimmy Kizza, Abel Kakuru, Moses R Kamya, Grant Dorsey, Philip J Rosenthal, Stephanie L Gaw","doi":"10.1080/15592294.2025.2475276","DOIUrl":"10.1080/15592294.2025.2475276","url":null,"abstract":"<p><p>Fetal growth restriction (FGR) is associated with perinatal death and adverse birth outcomes, as well as long-term complications, including increased childhood morbidity, abnormal neurodevelopment, and cardio-metabolic diseases in adulthood. Placental epigenetic reprogramming associated with FGR may mediate these long-term outcomes. Placental malaria (PM), characterized by sequestration of <i>Plasmodium falciparum</i>-infected erythrocytes in placental intervillous space, is the leading global cause of FGR, but its impact on placental epigenetics is unknown. We hypothesized that placental methylomic profiling would reveal common and distinct mechanistic pathways of non-malarial and PM-associated FGR. We analyzed placentas from a US cohort with no malaria exposure (<i>n</i> = 12) and a cohort from eastern Uganda, a region with a high prevalence of malaria (<i>n</i> = 12). From each site, 8 cases of FGR and 4 healthy controls were analyzed. PM was diagnosed by placental histopathology. We compared the methylation levels of over 850K CpGs of the placentas using Infinium MethylationEPIC v1 microarray. Non-malarial FGR was associated with 65 differentially methylated CpGs (DMCs), whereas PM-FGR was associated with 133 DMCs, compared to their corresponding controls without FGR. One DMC (cg16389901, located in the promoter region of <i>BMP4</i>) was commonly hypomethylated in both groups. We identified 522 DMCs between non-malarial FGR vs. PM-FGR placentas, independent of differing geographic location or cellular composition. Placentas with PM-associated FGR have distinct methylation profiles compared to placentas with non-malarial FGR, suggesting novel epigenetic reprogramming in response to malaria. Larger cohort studies are needed to determine the distinct long-term health outcomes in PM-associated FGR pregnancies.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2475276"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Analysis of HIV-1 subtypes and drug resistance mutations in people who inject drugs in Aizawl and nearby districts of Mizoram, India.
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-03-18 DOI: 10.1080/21505594.2025.2478074
Komal Raskar, Lal Thlengliani, Andrew Lalbiaknunga, Dipali Kale, Ajit Patil, Pragati Chavan, Richard Clr Hluna, Samiran Panda, Swarali Kurle
{"title":"Analysis of HIV-1 subtypes and drug resistance mutations in people who inject drugs in Aizawl and nearby districts of Mizoram, India.","authors":"Komal Raskar, Lal Thlengliani, Andrew Lalbiaknunga, Dipali Kale, Ajit Patil, Pragati Chavan, Richard Clr Hluna, Samiran Panda, Swarali Kurle","doi":"10.1080/21505594.2025.2478074","DOIUrl":"https://doi.org/10.1080/21505594.2025.2478074","url":null,"abstract":"<p><p>Over the last decade, there has been a steady increase in HIV-1 prevalence in Mizoram, India. Importantly, this increase in HIV-1 prevalence is not only limited to the key population groups such as female sex workers (FSWs) or people who inject drugs (PWID), and has been witnessed in general population as well. Injecting drug use has long been one of the key drivers of HIV-1 epidemic across the north-eastern states of India. In this study, using HIV-1 pol gene region sequences from Aizawl and adjoining districts, we examined the HIV-1 subtypes, recombinant forms, drug resistance mutations and also the spatiotemporal dynamics of the potential unique recombinant forms. In our dataset, the dominant subtype was HIV-1 subtype C (94.91%). We could also identify the presence of CRF01_AE (1.69%) and BC recombinant forms (3.39%). Drug resistance mutation analysis revealed that resistance against non-nucleoside reverse transcriptase inhibitors was most common in the sequences having any resistance mutations. Evolutionary analysis of unique BC recombinants estimated the most recent common ancestor of these sequences around 2004-2005 and them having an ancestry of United States of America (USA) origin.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2478074"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci.
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-04-03 DOI: 10.1080/15592294.2025.2487316
Yue Huo, Yaru Gao, Jiayi Ruan, Lingli Wang, Hongdong Li, Guini Hong
{"title":"A qualitative prognostic biomarker for melanoma based on the relative methylation orderings of CpG loci.","authors":"Yue Huo, Yaru Gao, Jiayi Ruan, Lingli Wang, Hongdong Li, Guini Hong","doi":"10.1080/15592294.2025.2487316","DOIUrl":"https://doi.org/10.1080/15592294.2025.2487316","url":null,"abstract":"<p><p>Skin cutaneous melanoma (SKCM) is an aggressive tumor with a poor prognosis. We developed SKCM-P8, a novel qualitative prognostic biomarker based on the relative methylation orderings of eight pairs of loci. Analysis of a training cohort and two independent validation datasets revealed a significant difference in overall survival between high- and low-risk groups stratified by SKCM-P8 (<i>p</i> < 0.05, log-rank test), with average area under the curve values of 0.83, 0.80, and 0.61, respectively. The differential methylation loci between high- and low-risk patients were enriched in immune-related biological processes and signaling pathways. Furthermore, low-risk patients exhibited higher CD8+ T cells and B levels, while high-risk patients had higher monocytes. The methylation levels of SKCM-P8 were also correlated with immune cell levels, indicating that they can reflect prognosis-related immune information. The low-risk group had a significantly higher mutation burden (<i>p</i> < 0.05, Wilcoxon test), suggesting potential benefits from immune checkpoint inhibitors. Patients stratified by SKCM-P8 displayed differential responses to therapy and immunotherapy (<i>p</i> < 0.05, Wilcoxon test), with low-risk patients showing better sensitivity and response. Furthermore, SKCM-P8 demonstrated super-predictive accuracy compared to six published models. Overall, SKCM-P8 offers a promising tool for predicting prognosis and guiding therapeutic decisions in SKCM.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2487316"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779511","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}
引用次数: 0
Disrupted adipokine secretion and inflammatory responses in human adipocyte hypertrophy.
IF 3.5 4区 生物学
Adipocyte Pub Date : 2025-12-01 Epub Date: 2025-04-03 DOI: 10.1080/21623945.2025.2485927
Dan Gao, Chen Bing, Helen R Griffiths
{"title":"Disrupted adipokine secretion and inflammatory responses in human adipocyte hypertrophy.","authors":"Dan Gao, Chen Bing, Helen R Griffiths","doi":"10.1080/21623945.2025.2485927","DOIUrl":"10.1080/21623945.2025.2485927","url":null,"abstract":"<p><p>Adipocyte hypertrophy is a critical contributor to obesity-induced inflammation and insulin resistance. This study employed a human adipocyte hypertrophy model to investigate the adipokine release, inflammatory responses, and the intracellular singling pathways. Hypertrophic adipocytes exhibited increased lipid content and lipolysis, a decline of anti-inflammatory adipokine adiponectin release and an increase of pro-inflammatory adipokine leptin release compared to mature adipocytes. Moreover, TNFα and LPS exacerbated the decrease in adiponectin secretion by hypertrophic adipocytes while promoting the secretion of leptin, MCP-1 and IL-6, which is associated with impaired activation of p38 and JNK MAPK and persistent activation of ERK and IκBα in hypertrophic adipocytes. These altered adipokine secretions and inflammatory responses within hypertrophic adipocytes may contribute to adipocyte dysfunction in human obesity.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2485927"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The LARP6 La module from Tetrabaena socialis reveals structural and functional differences from plant and animal LARP6 homologues.
IF 3.6 3区 生物学
RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-04-09 DOI: 10.1080/15476286.2025.2489303
Emily M Lewis, Olga Becker, Alexis N Symons, Cora LaCoss, A Jasmine Baclig, Avery Guzman, Charles Sanders, Leticia Gonzalez, Lisa R Warner, Karen A Lewis
{"title":"The LARP6 La module from <i>Tetrabaena socialis</i> reveals structural and functional differences from plant and animal LARP6 homologues.","authors":"Emily M Lewis, Olga Becker, Alexis N Symons, Cora LaCoss, A Jasmine Baclig, Avery Guzman, Charles Sanders, Leticia Gonzalez, Lisa R Warner, Karen A Lewis","doi":"10.1080/15476286.2025.2489303","DOIUrl":"10.1080/15476286.2025.2489303","url":null,"abstract":"<p><p>This study identified the LARP6 La Module from <i>Tetrabaena socialis</i> (<i>T. socialis</i>), a four-celled green algae, in an effort to better understand the evolution of LARP6 structure and RNA-binding activity in multicellular eukaryotes. Using a combination of sequence alignments, domain boundary screens, and structural modelling, we recombinantly expressed and isolated the <i>Ts</i>LARP6 La Module to > 98% purity for <i>in vitro</i> biochemical characterization. The La Module is stably folded and exerts minimal RNA binding activity against single-stranded homopolymeric RNAs. Surprisingly, it exhibits low micromolar binding affinity for the vertebrate LARP6 cognate ligand, a bulged-stem loop found in the 5'UTR of collagen type I mRNA, but does not bind double-stranded RNAs of similar size. These result suggests that the <i>Ts</i>LARP6 La Module may prefer structured RNA ligands. In contrast, however, the <i>Ts</i>LARP6 La Module does not exhibit the RNA chaperone activity that is observed in vertebrate homologs. Therefore, we conclude that protist LARP6 may have both distinct RNA ligands and binding mechanisms from the previously characterized LARP6 proteins of animals and vascular plants, thus establishing a distinct third class of the LARP6 protein family.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780999","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}
引用次数: 0
Evolution of the RNA alternative decay cis element into a high-affinity target for the immunomodulatory protein Roquin.
IF 3.6 3区 生物学
RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-01-13 DOI: 10.1080/15476286.2024.2448391
Jan-Niklas Tants, Katharina Friedrich, Jasmina Neumann, Andreas Schlundt
{"title":"Evolution of the RNA alternative decay <i>cis</i> element into a high-affinity target for the immunomodulatory protein Roquin.","authors":"Jan-Niklas Tants, Katharina Friedrich, Jasmina Neumann, Andreas Schlundt","doi":"10.1080/15476286.2024.2448391","DOIUrl":"https://doi.org/10.1080/15476286.2024.2448391","url":null,"abstract":"<p><p>RNA <i>cis</i> elements play pivotal roles in regulatory processes, e.g. in transcriptional and translational regulation. Two stem-looped <i>cis</i> elements, the constitutive and alternative decay elements (CDE and ADE, respectively) are shape-specifically recognized in mRNA 3' untranslated regions (UTRs) by the immune-regulatory protein Roquin. Roquin initiates mRNA decay and contributes to balanced transcript levels required for immune homoeostasis. While the interaction of Roquin with several CDEs is described, our knowledge about ADE complex formation is limited to the mRNA of <i>Ox40</i>, a gene encoding a T-cell costimulatory receptor. The <i>Ox40</i> 3'UTR comprises both a CDE and ADE, each sufficient for Roquin-mediated control. Opposed to highly conserved and abundant CDE structures, ADEs are rarer, but predicted to exhibit a greater structural heterogeneity. This raises the question of how and when two structurally distinct <i>cis</i> elements evolved as equal target motifs for Roquin. Using an interdisciplinary approach, we here monitor the evolution of sequence and structure features of the <i>Ox40</i> ADE across species. We designed RNA variants to probe en-detail determinants steering Roquin-RNA complex formation. Specifically, those reveal the contribution of a second RNA-binding interface of Roquin for recognition of the ADE basal stem region. In sum, our study sheds light on how the conserved Roquin protein selected ADE-specific structural features to evolve a second high-affinity mRNA target <i>cis</i> element relevant for adaptive immune regulation. As our findings also allow expanding the RNA target spectrum of Roquin, the approach can serve a paradigm for understanding RNA-protein specificity through back-tracing the evolution of the RNA element.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
DNA-based cell typing in menstrual effluent identifies cell type variation by sample collection method: toward noninvasive biomarker development for women's health. 基于dna的月经流出液细胞分型通过样本收集方法识别细胞类型变化:面向女性健康的无创生物标志物开发。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-01-18 DOI: 10.1080/15592294.2025.2453275
Irma M Vlasac, Hannah G Stolrow, Zaneta M Thayer, Brock C Christensen, Luisa Rivera
{"title":"DNA-based cell typing in menstrual effluent identifies cell type variation by sample collection method: toward noninvasive biomarker development for women's health.","authors":"Irma M Vlasac, Hannah G Stolrow, Zaneta M Thayer, Brock C Christensen, Luisa Rivera","doi":"10.1080/15592294.2025.2453275","DOIUrl":"https://doi.org/10.1080/15592294.2025.2453275","url":null,"abstract":"<p><p>Menstrual effluent cell profiles have potential as noninvasive biomarkers of female reproductive and gynecological health and disease. We used DNA methylation-based cell type deconvolution (methylation cytometry) to identify cell type profiles in self-collected menstrual effluent. During the second day of their menstrual cycle, healthy participants collected menstrual effluent using a vaginal swab, menstrual cup, and pad. Immune cell proportions were highest in menstrual cup samples, and epithelial cells were highest in swab samples. Our work demonstrates the feasibility and utility of menstrual effluent cell profiling in population-level research using remotely collected samples and DNA methylation.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2453275"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002103","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}
引用次数: 0
Identification of deleterious non-synonymous single nucleotide polymorphisms in the mRNA decay activator ZFP36L2. mRNA衰变激活子ZFP36L2中有害非同义单核苷酸多态性的鉴定。
IF 3.6 3区 生物学
RNA Biology Pub Date : 2025-12-01 Epub Date: 2024-12-13 DOI: 10.1080/15476286.2024.2437590
Betül Akçeşme, Hilal Hekimoğlu, Venkat R Chirasani, Şeyma İş, Habibe Nur Atmaca, Justin M Waldern, Silvia B V Ramos
{"title":"Identification of deleterious non-synonymous single nucleotide polymorphisms in the mRNA decay activator ZFP36L2.","authors":"Betül Akçeşme, Hilal Hekimoğlu, Venkat R Chirasani, Şeyma İş, Habibe Nur Atmaca, Justin M Waldern, Silvia B V Ramos","doi":"10.1080/15476286.2024.2437590","DOIUrl":"10.1080/15476286.2024.2437590","url":null,"abstract":"<p><p>More than 4,000 single nucleotide polymorphisms (SNP) variants have been identified in the human <i>ZFP36L2</i> gene, however only a few have been studied in the context of protein function. The tandem zinc finger domain of ZFP36L2, an RNA binding protein, is the functional domain that binds to its target mRNAs. This protein/RNA interaction triggers mRNA degradation, controlling gene expression. We identified 32 non-synonymous SNPs (nsSNPs) in the tandem zinc finger domain of ZFP36L2 that could have possible deleterious impacts in humans. Using different bioinformatic strategies, we prioritized five among these 32 nsSNPs, namely rs375096815, rs1183688047, rs1214015428, rs1215671792 and rs920398592 to be validated. When we experimentally tested the functionality of these protein variants using gel shift assays, all five (Y154H, R160W, R184C, G204D, and C206F) resulted in a dramatic reduction in RNA binding compared to the WT protein. To understand the mechanistic effect of these variants on the protein/RNA interaction, we employed DUET, DynaMut and PyMOL to investigate structural changes in the protein. Additionally, we conducted Molecular Docking and Molecular Dynamics Simulations to fine tune the active behaviour of this biomolecular system at an atomic level. Our results propose atomic explanations for the impact of each of these five genetic variants identified.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":"22 1","pages":"1-15"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819035","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}
引用次数: 0
M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury.
IF 5.2 2区 生物学
Redox Report Pub Date : 2025-12-01 Epub Date: 2025-01-27 DOI: 10.1080/13510002.2025.2454892
Qiong Jiang, Xuehai Chen, Kezeng Gong, Zhe Xu, Lianglong Chen, Feilong Zhang
{"title":"M6a demethylase FTO regulates the oxidative stress, mitochondrial biogenesis of cardiomyocytes and PGC-1a stability in myocardial ischemia-reperfusion injury.","authors":"Qiong Jiang, Xuehai Chen, Kezeng Gong, Zhe Xu, Lianglong Chen, Feilong Zhang","doi":"10.1080/13510002.2025.2454892","DOIUrl":"10.1080/13510002.2025.2454892","url":null,"abstract":"<p><strong>Objective: </strong>Myocardial ischemia-reperfusion injury (MIRI) is a highly complex disease with high morbidity and mortality. Studying the molecular mechanism of MIRI and discovering new targets are crucial for the future treatment of MIRI.</p><p><strong>Methods: </strong>We constructed the MIRI rat model and hypoxia/reoxygenation (H/R) injury cardiomyocytes model. RT-PCR and Western blot were used to investigate the expression of the fat mass and obesity-associated (FTO) gene. Electrocardiogram, echocardiography, triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to assess the model and the effect of FTO overexpression. The generation of reactive oxygen species (ROS) and the levels of superoxide dismutase (SOD2), mitochondrial transcription factor (TFAM) and cytochrome c oxidase I (COXI) were detected to assess the oxidative stress and mitochondrial biogenesis. RNA immunoprecipitation (RIP) and RNA pulldown assays were used to identify the interaction of FTO and PGC-1a. The m6A dot blot, methylated RNA immunoprecipitation PCR (MeRIP-PCR) and RNA stability analysis were used to analyze the regulation of methylation of PGC-1a by FTO.</p><p><strong>Results: </strong>FTO was downregulated in MIRI rats and H/R induced cardiomyocytes. Overexpression of FTO inhibited ROS level and increased the expression of SOD2, TFAM and COXI in vitro and in vivo. In addition, PGC-1a was identified as a downstream target of FTO. FTO enhanced the stability of PGC-1a mRNA through removing the m6A modification.</p><p><strong>Conclusion: </strong>Our study revealed the role of FTO regulates the oxidative stress and mitochondrial biogenesis via PGC-1a in MIRI, which may provide a new approach to mitigating MIRI.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2454892"},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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