Functional & Integrative Genomics最新文献

{"title":"Comprehensive study of tRNA-derived fragments in plants for biotic stress responses","authors":"Supriya P. Swain,&nbsp;Niyati Bisht,&nbsp;Shailesh Kumar","doi":"10.1007/s10142-025-01576-3","DOIUrl":"10.1007/s10142-025-01576-3","url":null,"abstract":"<div><p>Plant growth and development are often disrupted by biological stressors as they interfere with the regulatory pathways. Among the key regulators, transfer-RNA-derived fragments (tRFs) have emerged as key players in plant defense mechanisms. While tRF-mediated responses to abiotic stress have been well studied, their role in biotic stress remains less understood, as various stressors may elicit different regulatory systems. In this study, tRF-mediated biotic responses in three species, viz. <i>Arabidopsis thaliana, Oryza sativa,</i> and <i>Solanum lycopersicum</i> are investigated using <i>in-silico</i> approaches. Analysis of predicted tRFs across various biotic stress conditions reveals specific interactions with mRNA targets, microRNAs (miRNAs), and transposable elements (TEs), highlighting their regulatory significance in plant adaptation mechanisms. These findings provide new insights into tRF-mediated stress responses and establish a computational framework for further functional studies. The study’s database is publicly available at http://www.nipgr.ac.in/PbtRFdb.\u0000</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143688525","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}

{"title":"Linking genomic and proteomic signatures to brain amyloid burden: insights from GR@ACE/DEGESCO","authors":"Raquel Puerta,&nbsp;Itziar de Rojas,&nbsp;Pablo García-González,&nbsp;Clàudia Olivé,&nbsp;Oscar Sotolongo-Grau,&nbsp;Ainhoa García-Sánchez,&nbsp;Fernando García-Gutiérrez,&nbsp;Laura Montrreal,&nbsp;Juan Pablo Tartari,&nbsp;Ángela Sanabria,&nbsp;Vanesa Pytel,&nbsp;Carmen Lage,&nbsp;Inés Quintela,&nbsp;Nuria Aguilera,&nbsp;Eloy Rodriguez-Rodriguez,&nbsp;Emilio Alarcón-Martín,&nbsp;Adelina Orellana,&nbsp;Pau Pastor,&nbsp;Jordi Pérez-Tur,&nbsp;Gerard Piñol-Ripoll,&nbsp;Adolfo López de Munain,&nbsp;Jose María García-Alberca,&nbsp;Jose Luís Royo,&nbsp;María J. Bullido,&nbsp;Victoria Álvarez,&nbsp;Luis Miguel Real,&nbsp;Arturo Corbatón Anchuelo,&nbsp;Dulcenombre Gómez-Garre,&nbsp;María Teresa Martínez Larrad,&nbsp;Emilio Franco-Macías,&nbsp;Pablo Mir,&nbsp;Miguel Medina,&nbsp;Raquel Sánchez-Valle,&nbsp;Oriol Dols-Icardo,&nbsp;María Eugenia Sáez,&nbsp;Ángel Carracedo,&nbsp;Lluís Tárraga,&nbsp;Montse Alegret,&nbsp;Sergi Valero,&nbsp;Marta Marquié,&nbsp;Mercè Boada,&nbsp;Pascual Sánchez Juan,&nbsp;Jose Enrique Cavazos,&nbsp;Alfredo Cabrera-Socorro,&nbsp;Amanda Cano,&nbsp;Agustín Ruiz,&nbsp;for the Alzheimer’s Disease Neuroimaging Initiative","doi":"10.1007/s10142-025-01581-6","DOIUrl":"10.1007/s10142-025-01581-6","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is a complex disease with a strong genetic component, yet many genetic risk factors remain unknown. We combined genome-wide association studies (GWAS) on amyloid endophenotypes measured in cerebrospinal fluid (CSF) and positron emission tomography (PET) as surrogates of amyloid pathology, which may provide insights into the underlying biology of the disease. We performed a meta-GWAS of CSF Aβ42 and PET measures combining six independent cohorts (<i>n</i> = 2,076). Given the opposite beta direction of Aβ phenotypes in CSF and PET measures, only genetic signals showing opposite directions were considered for analysis (<i>n</i> = 376,599). We explored the amyloidosis signature in the CSF proteome using SOMAscan proteomics (ACE cohort, <i>n</i> = 1,008), connected it with GWAS loci modulating amyloidosis and performed an enrichment analysis of overlapping hits. Finally, we compared our results with a large meta-analysis using publicly available datasets in CSF (<i>n</i> = 13,409) and PET (<i>n</i> = 13,116). After filtering the meta-GWAS, we observed genome-wide significance in the rs429358-<i>APOE</i> locus and annotated nine suggestive hits. We replicated the <i>APOE</i> loci using the large CSF-PET meta-GWAS, identifying multiple AD-associated genes including the novel <i>GADL1</i> locus. Additionally, we found 1,387 FDR-significant SOMAscan proteins associated with CSF Aβ42 levels. The overlap among GWAS loci and proteins associated with amyloid burden was minimal (<i>n</i> = 35). The enrichment analysis revealed mechanisms connecting amyloidosis with the plasma membrane’s anchored component, synapse physiology and mental disorders that were replicated in the large CSF-PET meta-analysis. Combining CSF and PET amyloid GWAS with CSF proteome analyses may effectively elucidate causative molecular mechanisms behind amyloid mobilization and AD physiopathology.\u0000</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01581-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New approaches of chimeric antigen receptor (CAR)-immune cell-based therapy in gastric cancer; highlight CAR-T and CAR-NK","authors":"Saade Abdalkareem Jasim,&nbsp;Harikumar Pallathadka,&nbsp;G. V. Sivaprasad,&nbsp;Ashwani Kumar,&nbsp;Yasser Fakri Mustafa,&nbsp;Jaafaru Sani Mohammed,&nbsp;Mamdouh Eldesoqui,&nbsp;Atreyi Pramanik,&nbsp;Rakhimova Khusnidakhon Abdukarimovna,&nbsp;Ahmed Hussein Zwamel","doi":"10.1007/s10142-025-01584-3","DOIUrl":"10.1007/s10142-025-01584-3","url":null,"abstract":"<div><p>One characteristic that makes gastric cancer (GC) against other cancers is the intricate immune system's reaction, particularly to tenacious inflammation. Consequently, the immunological function is essential to the growth of this malignancy. Tumor immunotherapy has yielded several encouraging outcomes, but despite this, different patients continue to not respond to treatment, and a far larger number become resistant to it. Also, activated CAR-T cells express a majority of immunological checkpoint factors, containing PD1, CTLA4, and LAG3, which counteracts the anti-tumor actions of CAR-T cells. Moreover, cytokine release syndrome is one of the possible adverse responses of CAR-T cell therapy. Therefore, producing universal allogeneic T lymphocytes with potent anti-tumor activity is essential. This study demonstrates current research on this cutting-edge technology, including the composition and mode of action of CAR-NK and CAR-T cells in GC. Also, in this study, we examined recent studies about various specific GC biomarkers that target CAR-T cells and CAR-NK cells.\u0000</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698678","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}

{"title":"Correction to: Integrative single-cell and bulk RNA-seq analysis identifies lactylation-related signature in osteosarcoma","authors":"Zhou Xie,&nbsp;Xiao Qu,&nbsp;Jun Zhang,&nbsp;Yanran Huang,&nbsp;Runhan Zhao,&nbsp;Dagang Tang,&nbsp;Ningdao Li,&nbsp;Zhule Wang,&nbsp;Xiaoji Luo","doi":"10.1007/s10142-025-01589-y","DOIUrl":"10.1007/s10142-025-01589-y","url":null,"abstract":"","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676316","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}

{"title":"DUBR non-coding RNA regulates gene expression by affecting AP-1 enhancer accessibility","authors":"Simone D. Hall,&nbsp;Khoa Tran,&nbsp;Jonathan Zhu,&nbsp;Tong Su,&nbsp;Colleen A. McHugh","doi":"10.1007/s10142-025-01582-5","DOIUrl":"10.1007/s10142-025-01582-5","url":null,"abstract":"<div><p>Non-coding RNAs (ncRNAs) are finely tuned cellular regulators important for human cell growth and cancer progression. DUBR (<i>Dppa2</i> upstream binding RNA, also known as linc00883) is a nuclear ncRNA first discovered in mice for its role in regulating myoblast differentiation through interactions with chromatin and DNA methyltransferases. High expression levels of this ncRNA are predictive of poor patient outcome in colon adenocarcinoma, suggesting that DUBR may be involved in controlling cancer growth. To elucidate its function, we used RAP-MS and RNA immunoprecipitation techniques which revealed its interaction with epigenetic maintenance proteins in the human colon cancer cell line HCT116. Further, ATAC-seq and RNA-seq were used to address its function in regulating the epigenome and transcriptome of HCT116 cells. Here we report that DUBR is a regulator of human colon cancer cell line HCT116 survival. Additionally, we find that the ncRNA DUBR regulates AP-1 transcription factor binding site accessibility at enhancers of genes involved in differentiation and morphogenesis through interactions with epigenetic proteins such as NuRD complex members HDAC1 and CHD4.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01582-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CutIn: a ready-to-use construct for rapid generation of urgently needed transgenic cell lines in emerging infection research","authors":"Liangliang Zhang,&nbsp;Dandan Li,&nbsp;Xiaowei Li,&nbsp;Liang Zong,&nbsp;Haibo Bian,&nbsp;Junnan Lu","doi":"10.1007/s10142-025-01566-5","DOIUrl":"10.1007/s10142-025-01566-5","url":null,"abstract":"<div><p>Site-directed exogenous gene knock-in for stable cell line generation remains a multi-step procedure that heavily relies on expertise. Therefore, there is a need for a competent and easily manageable method, particularly when there is an urgent demand for cell lines, especially for emerging infection research. We present here a universal construct called CutIn that expresses the Cas9 protein and dual sgRNAs targeting a host cell genome locus and the ampicillin resistance (<i>AmpR</i>) gene of a cotransfected donor plasmid commercially available. This construct specifically induces double-strand breaks (DSBs) in cotransfected plasmids and host cell genomes, thereby facilitating whole plasmid integration through nonhomologous end joining (NHEJ) repair mechanisms. As pilot tests, adeno-associated virus integration site 1 (<i>AAVS1</i>) or hypoxanthine phosphoribosyl transferase (<i>HPRT</i>) locus was selected as host genome target, commonly used human cell lines 293T, HeLa and HCT116 were employed. CutIn was subjected for reporter plasmid knock-in in all three cell lines, either <i>AAVS1</i> and <i>AmpR</i> or <i>HPRT</i> and <i>AmpR</i> loci were efficiently targeted. Fluorescent protein, human angiotensin-converting enzyme 2 (ACE2) and dengue virus (DENV) infection reporter transgenic cells were rapidly obtained via CutIn-mediated whole expression vector integration. This method is designed to be user-friendly and shows potential for supporting the investigation of emerging/re-emerging infectious diseases. Further validation in diverse research contexts will be necessary to fully assess its applicability and effectiveness.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655387","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}

{"title":"Discovery of circular transcripts of the human BCL2-like 12 (BCL2L12) apoptosis-related gene, using targeted nanopore sequencing, provides new insights into circular RNA biology","authors":"Paraskevi Karousi,&nbsp;Christos K. Kontos,&nbsp;Stavroula T. Nikou,&nbsp;Thomas Carell,&nbsp;Diamantis C. Sideris,&nbsp;Andreas Scorilas","doi":"10.1007/s10142-025-01578-1","DOIUrl":"10.1007/s10142-025-01578-1","url":null,"abstract":"<div><p>Circular RNAs (circRNAs) constitute an RNA type formed by back-splicing. <i>BCL2-like 12</i> (<i>BCL2L12</i>) is an apoptosis-related gene comprising 7 exons. In this study, we used targeted nanopore sequencing to identify circular <i>BCL2L12</i> transcripts in human colorectal cancer cells and investigated the effect of circRNA silencing on mRNA expression of the parental gene. In brief, nanopore sequencing following nested PCR amplification of cDNAs of <i>BCL2L12</i> circRNAs from 7 colorectal cancer cell lines unraveled 46 <i>BCL2L12</i> circRNAs, most of which described for the first time. Interestingly, 40 novel circRNAs are likely to form via back-splicing between non-canonical back-splice sites residing in highly similar regions of the primary transcripts. All back-splice junctions were validated using next-generation sequencing (NGS) after circRNA enrichment. Surprisingly, 2 novel circRNAs also comprised a poly(A) tract after <i>BCL2L12</i> exon 7; this poly(A) tract was back-spliced to exon 1, in both cases. Furthermore, the selective silencing of a <i>BCL2L12</i> circRNA resulted in a subsequent decrease of <i>BCL2L12</i> mRNA levels in HCT 116 cells, thus providing evidence of parental gene expression regulation by circRNAs. In conclusion, our study led to the discovery of many circular transcripts from a single human gene and provided new insights into circRNA biogenesis and mode of action.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01578-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NEDD4 facilitates the progression of endometrial carcinoma by enhancing PAMR1 protein degradation through ubiquitination","authors":"Hongbo Guo,&nbsp;Hongping Tang,&nbsp;Yihui Yang,&nbsp;Hui Xu,&nbsp;Jiaqi Fan,&nbsp;Shuxia Chen,&nbsp;Lingxiu Hou,&nbsp;Ying Yuan,&nbsp;Guangwu Zhang","doi":"10.1007/s10142-025-01567-4","DOIUrl":"10.1007/s10142-025-01567-4","url":null,"abstract":"<div><p>Endometrial carcinoma (EC) is an epithelial malignant neoplasm that frequently appears in postmenopausal and perimenopausal women. PAMR1 is related to the prognosis of EC. Here, we probed into the significance of PAMR1 in EC progression and its acting mechanism. In silico analysis was conducted to identify the differentially expressed gene PAMR1 and its upstream gene NEDD4 in EC, followed by the determination of their expression in EC tissues and cells. The gene expression, cell proliferation, angiogenesis, migration, invasion, and apoptosis were examined after ectopic expression or knockdown experiments. The interaction between NEDD4 and PAMR1 and the level of PAMR1 ubiquitination were examined. The injection of Ishikawa cell suspensions into nude mice was carried out to establish a tumor xenograft model, validating the roles of PAMR1 and NEDD4 in EC. EC cells exhibited high NEDD4 expression and low PAMR1 expression. NEDD4 knockdown or PAMR1 overexpression suppressed the invasive, migrating, angiogenic, and proliferative properties of EC cells while promoting apoptosis. NEDD4 facilitated PAMR1 protein degradation through ubiquitination. Deletion of PAMR1 abolished the inhibitory effects of NEDD4 knockdown on the malignant behaviors of EC cells. Furthermore, NEDD4 knockdown restrained EC growth in nude mice by increasing PAMR1 protein expression. NEDD4 facilitated EC progression by enhancing PAMR1 protein degradation through ubiquitination.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622235","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}

{"title":"Single-cell RNA sequencing revealed changes in the tumor microenvironment induced by radiotherapy for cervical cancer and the molecular mechanism of mast cells in immunosuppression","authors":"Lujiadai Xue,&nbsp;Linzhi Gao,&nbsp;Shimin Zhou,&nbsp;Chaofan Yan,&nbsp;Xian Zhang,&nbsp;Wei Lin,&nbsp;Hu Li,&nbsp;Yuan Shen,&nbsp;Xiaoyu Wang","doi":"10.1007/s10142-025-01564-7","DOIUrl":"10.1007/s10142-025-01564-7","url":null,"abstract":"<div><p>Radiotherapy (RT) is an important treatment for cervical cancer (CC), effectively controlling tumor growth and improving survival rates. However, radiotherapy-induced cell heterogeneity and its underlying mechanisms remain unclear, which may potentially impact treatment efficacy. This study aims to investigate tumor microenvironment changes following radiotherapy for CC, hoping to provide evidence to improve the therapeutic effects of radiotherapy. For the first time, we applied single-cell RNA sequencing (scRNA-seq) to analyze tissue samples from three CC patients pre- and post-radiotherapy. We obtained gene expression data from 52,506 cells to identify the cellular changes and molecular mechanisms induced by radiotherapy. Radiotherapy significantly alters cellular composition and gene expression within the tumor microenvironment (TME), notably upregulating mast cell expression. Mast cells are involved in multiple cell axes in the CC ecosystem after radiotherapy, and play a pivotal role in tumor immunosuppression and matrix remodeling. scRNA-seq revealed gene expression variations among cell types after radiotherapy, underscoring the importance of specific cell types in modulating the TME post-treatment. This study revealed the molecular mechanism of radiotherapy for CC and the role of mast cells, providing a foundation for optimizing the personalized treatment of CC.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612259","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}

{"title":"Combined transcriptomic and proteomic analyses reveal relevant myelin features in mice with ischemic stroke","authors":"Qiuyang Qian,&nbsp;Hao Lyu,&nbsp;Wei Wang,&nbsp;Qiwen Wang,&nbsp;Desheng Li,&nbsp;Xiaojia Liu,&nbsp;Yi He,&nbsp;Mei Shen","doi":"10.1007/s10142-025-01573-6","DOIUrl":"10.1007/s10142-025-01573-6","url":null,"abstract":"<div><p>Ischemic stroke (IS), a leading cause of global disability and mortality, is characterized by white matter damage and demyelination. Despite advances, the molecular mechanisms driving post-IS myelin pathology remain poorly understood, limiting therapeutic development. This study investigates key myelin-related genes (MRGs) and their regulatory networks to identify novel therapeutic targets. A transient middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice, with brain tissues collected at four timepoints (Sham0D, MCAO0D, MCAO7D, MCAO14D). Transcriptomic and proteomic sequencing were performed, followed by soft clustering (Mfuzz), functional enrichment (GO/KEGG), and ROC analysis to identify key MRGs. Competing endogenous RNA (ceRNA) networks were constructed, and drug prediction was conducted using the Comparative Toxicogenomics Database (CTD) and molecular docking. Expression validation was performed via qRT-PCR and Western blot. Integrated multi-omics analysis identified <i>Wasf3</i> and <i>Slc25a5</i> as key MRGs, enriched in mitochondrial respiration, calcium metabolism, and cytoskeletal regulation. The AUC values of the one-to-one model scores were all greater than 0.7, suggesting that <i>Wasf3</i> and <i>Slc25a5</i> were able to effectively discriminate between samples from different time points. A ceRNA network revealed critical interactions, including the <i>Wasf3-mmu-miR-423-5p-H19</i> axis, linking apoptosis and myelin dysfunction. Drug prediction highlighted valproic acid (VPA) as a high-affinity binder for both genes (binding energies: − 4.2 and − 4.7 kcal/mol), suggesting its potential as a therapeutic candidate for IS. Experimental validation confirmed significant downregulation of <i>Wasf3</i> mRNA (<i>p</i> &lt; 0.01) and protein (<i>p</i> = 0.069) post-IS, while <i>Slc25a5</i> showed no significant changes, potentially due to sample size limitations. This study establishes <i>Wasf3</i> and <i>Slc25a5</i> as pivotal regulators of post-IS myelin pathology and proposes VPA as a promising therapeutic candidate to enhance remyelination. The findings underscore the utility of multi-omics approaches in bridging molecular mechanisms to clinical translation, offering new strategies for IS diagnosis and treatment.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01573-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}