BMC Genomics最新文献

{"title":"Predicting substrates for orphan solute carrier proteins using multi-omics datasets.","authors":"Y Zhang, S Newstead, P Sarkies","doi":"10.1186/s12864-025-11330-5","DOIUrl":"10.1186/s12864-025-11330-5","url":null,"abstract":"<p><p>Solute carriers (SLC) are integral membrane proteins responsible for transporting a wide variety of metabolites, signaling molecules and drugs across cellular membranes. Despite key roles in metabolism, signaling and pharmacology, around one third of SLC proteins are 'orphans' whose substrates are unknown. Experimental determination of SLC substrates is technically challenging, given the wide range of possible physiological candidates. Here, we develop a predictive algorithm to identify correlations between SLC expression levels and intracellular metabolite concentrations by leveraging existing cancer multi-omics datasets. Our predictions recovered known SLC-substrate pairs with high sensitivity and specificity compared to simulated random pairs. CRISPR-Cas9 dependency screen data and metabolic pathway adjacency data further improved the performance of our algorithm. In parallel, we combined drug sensitivity data with SLC expression profiles to predict new SLC-drug interactions. Together, we provide a novel bioinformatic pipeline to predict new substrate predictions for SLCs, offering new opportunities to de-orphanise SLCs with important implications for understanding their roles in health and disease.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"130"},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390002","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}

{"title":"Transcriptome and WGCNA reveals the potential genetic basis of photoperiod-sensitive male sterility in soybean.","authors":"Yuhua Yang, Suqin He, Lihong Xu, Minggui Wang, Shuichun Chen, Zhiyuan Bai, Tingting Yang, Bo Zhao, Lixiang Wang, Haiping Zhang, Jiangjiang Zhang, Ruijun Zhang","doi":"10.1186/s12864-025-11314-5","DOIUrl":"10.1186/s12864-025-11314-5","url":null,"abstract":"<p><strong>Background: </strong>Soybean (Glycine max (L.) Merr.) is a crucial crop due to its high plant protein and oil content. Previous studies have shown that soybeans exhibit significant heterosis in terms of yield and protein content However, the practical application of soybean heterosis remains difficult, as the molecular mechanisms underlying photoperiod-sensitive genic male sterile (PGMS) is still unclear.</p><p><strong>Results: </strong>This study characterized the PGMS line 88-428BY, which is sterile under short-day (SD) conditions and fertile under long-day (LD) conditions. To elucidate the genetic basis for this trait, we collected anthers, from 88-428BY under SD and LD conditions at three developmental stages, resulting in the identification of differentially expressed genes (DEGs) (2333, 2727 and 7282 DEGs, respectively) using Illumina transcriptome analysis. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, we fund that among the DEGs, enriched genes were associated with photoperiod stress, light stimulus, oxidation-reduction processes, multicellular organism development and protein phosphorylation. Additionally, weighted correlation network analysis identified four modules (blue, brown, red, and yellow) that were significantly correlated with PGMS, revealing co-expressed hub genes with potential regulatory roles. Functional annotation of 224 DEGs with|KME| >0.9 across the four modules in seven databases highlighted their involvement in light stimulus, oxidation-reduction processes, multicellular organism development, and protein phosphorylation, suggesting their importance in soybean PGMS. By integrating fertility-related genes previously identified by other studies with the DEGs from our analysis, we identified eight candidate genes associated with the photosensitive sterility in soybeans.</p><p><strong>Conclusions: </strong>This study enhances the understanding of PGMS in soybean and establishes the genetic basis for a two-line hybrid seed production system in soybean.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"131"},"PeriodicalIF":3.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11816801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398033","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}

{"title":"Full-length transcriptome assembly and RNA-Seq integration of diploid and tetraploid ryegrass to investigate differences in cd uptake and accumulation among ryegrass with different ploidy levels.","authors":"Xunzhe Yang, Xia Wang, Xuan Zhang, Dandan Wu, Yiran Cheng, Yi Wang, Lina Sha, Jian Zeng, Houyang Kang, Xing Fan, Linkai Huang, Yinglong Chen, Yonghong Zhou, Haiqin Zhang","doi":"10.1186/s12864-025-11325-2","DOIUrl":"10.1186/s12864-025-11325-2","url":null,"abstract":"<p><strong>Background: </strong>The accumulation of cadmium (Cd) in ryegrass (Lolium multiflorum Lamk.) as a widely used pasture plant poses a serious risk to food safety. This study aimed to investigate the differences in phenotypes, physiology, and expression of metal transporters between four ryegrass genotypes (diploid/tetraploid and Cd-tolerant/sensitive).</p><p><strong>Results: </strong>The diploid/Cd-sensitive genotypes were found to uptake, accumulate, and translocate more Cd compared to the tetraploid/Cd-tolerant genotypes. Cd with more soluble components facilitated the transfer of Cd from root to shoot in the sensitive genotypes. Tetraploid and Cd-tolerant Chuansi No.1 accumulated less Cd in shoots but higher ratio in root cell wall, making it a promising model for studying the mechanisms of plant resistance to Cd stress. The complex regulatory system and dilution effect contributed to the lower uptake and accumulation of Cd in tetraploid genotypes. Moreover, tetraploid genotypes exhibited higher expression of genes that promoted Cd efflux, which could contribute to their lower Cd accumulation.</p><p><strong>Conclusions: </strong>Overall, this study sheds light on the physiological and transcriptional mechanisms of Cd uptake and accumulation by different polyploids, providing guidance for ryegrass breeding and soil improvement.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"128"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389919","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}

{"title":"Genome-wide analysis of the FKBP gene family and the potential role of GhFKBP 13 in chloroplast biogenesis in upland cotton.","authors":"Jianguang Liu, Zhao Geng, Guiyuan Zhao, Mengzhe Li, Zetong An, Hanshuang Zhang, Yongqiang Wang","doi":"10.1186/s12864-025-11293-7","DOIUrl":"10.1186/s12864-025-11293-7","url":null,"abstract":"<p><strong>Background: </strong>In plants, FK506-binding proteins (FKBPs) have been shown to participate in various biological processes such as photosynthetic system reaction, stress response, and growth and development. However, the roles of FKBPs in cotton are less well known.</p><p><strong>Results: </strong>In this study, we investigated FKBP family genes on a genome-wide scale in four Gossypium species. A total of 147 FKBP genes were identified from these four Gossypium species and placed into three classes based on phylogenetic analysis. Collinearity analysis indicated that whole-genome duplication events and segmental duplication events were the main sources of gene amplification during the evolution of FKBP genes. Conserved motif, expression profiles and cis-acting elements prediction of the GhFKBPs analysis revealed that GhFKBPs were differentially expressed in different tissues and under abiotic stress. qRT-PCR analysis showed that some GhFKBPs were predominantly expressed in leaves. The analysis of cis-acting elements prediction revealed that MYB, MYC and ERE related binding sites in the promoters of GhFKBP genes were the most abundant. Furthermore, the composition and distribution of these cis-acting elements exhibited differences between homologous GhFKBP gene pairs. Silencing of GhFKBP13 in cotton resulted in disruption of chloroplast structure and starch metabolism disorders.</p><p><strong>Conclusions: </strong>Taken together, 147 FKBP family genes in four Gossypium species are comprehensively characterized, and GhFKBP13 play a critical role in chloroplast biogenesis in upland cotton.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"125"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389938","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}

{"title":"Gene-based Hardy-Weinberg equilibrium test using genotype count data: application to six types of cancers.","authors":"Jo Nishino, Fuyuki Miya, Mamoru Kato","doi":"10.1186/s12864-025-11321-6","DOIUrl":"10.1186/s12864-025-11321-6","url":null,"abstract":"<p><strong>Background: </strong>An alternative approach to investigate associations between genetic variants and disease is to examine deviations from the Hardy-Weinberg equilibrium (HWE) in genotype frequencies within a case population, instead of case-control association analysis. The HWE analysis requires disease cases and demonstrates a notable ability in mapping recessive variants. Allelic heterogeneity is a common phenomenon in diseases. While gene-based case-control association analysis successfully incorporates this heterogeneity, there are no such approaches for HWE analysis. Therefore, we proposed a gene-based HWE test (gene-HWT) by aggregating single-nucleotide polymorphism (SNP)-level HWE test statistics in a gene to address allelic heterogeneity.</p><p><strong>Results: </strong>This method used only genotype count data and publicly available linkage disequilibrium information and has a very low computational cost. Extensive simulations demonstrated that gene-HWT effectively controls the type I error at a low significance level and outperforms SNP-level HWE test in power when there are multiple causal variants within a gene. Using gene-HWT, we analyzed genotype count data from a genome-wide association study of six cancer types in Japanese individuals and suggest DGKE and ANO3 as potential germline factors in colorectal cancer. Furthermore, FSTL4 was suggested through a combined analysis across the six cancer types, with particularly notable associations observed in colorectal and prostate cancers.</p><p><strong>Conclusions: </strong>These findings indicate the potential of gene-HWT to elucidate the genetic basis of complex diseases, including cancer.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"124"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389930","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}

{"title":"Whole-genome relaxed selection and molecular constraints in Triplophysa under adapted Qinghai-Tibetan Plateau.","authors":"Qingyuan Zhao, Fei Xie, Qiuyue He, Lulu Wang, Kenan Guo, Cong Zhang, Yong Wang","doi":"10.1186/s12864-025-11290-w","DOIUrl":"10.1186/s12864-025-11290-w","url":null,"abstract":"<p><p>High-altitude environments are inhospitable, but Triplophysa, the largest taxon among the three major fish groups in the Qinghai-Tibetan Plateau (QTP), is an exception. However, the evolutionary profiling of the common ancestor and its contribution to the adaptation of existing QTP native species is unclear.We researched the comparative genomics of Triplophysa species and found that the genome-wide genes of Triplophysa and its ancestry have the characteristics of rapid evolution.Moreover, the rapid evolution of the ancestral genes was caused by relaxed selection. Natural selection analysis showed that more ancestral relaxed selection genes were under strongly purifying selection and showed higher expression in QTP endemic Triplophysa species.The change in natural selection might be associated with the adaptation to QTP. It should be noted that SPT5 homolog, DSIF elongation factor subunit (supt5h) experienced relaxed selection in common ancestral populations of Triplophysa but under purifying selection in extant species, which might be related to hypoxia adaptation of QTP. In summary, the extant species in different environments were used to infer the evolutionary profile of the common ancestor and to identify candidate genes based on changes in natural selection. Our work might provide new clues for understanding adaptation to extreme environments.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"123"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381462","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}

{"title":"Nanopore adaptive sampling to identify the NLR gene family in melon (Cucumis melo L.).","authors":"Javier Belinchon-Moreno, Aurélie Berard, Aurélie Canaguier, Véronique Chovelon, Corinne Cruaud, Stéfan Engelen, Rafael Feriche-Linares, Isabelle Le-Clainche, William Marande, Vincent Rittener-Ruff, Jacques Lagnel, Damien Hinsinger, Nathalie Boissot, Patricia Faivre-Rampant","doi":"10.1186/s12864-025-11295-5","DOIUrl":"10.1186/s12864-025-11295-5","url":null,"abstract":"<p><strong>Background: </strong>Nanopore adaptive sampling (NAS) offers a promising approach for assessing genetic diversity in targeted genomic regions. Here we designed and validated an experiment to enrich a set of resistance genes in several melon cultivars as a proof of concept.</p><p><strong>Results: </strong>Using the same reference to guide read acceptance or rejection with NAS, we successfully and accurately reconstructed the 15 regions in two newly assembled ssp. melo genomes and in a third ssp. agrestis cultivar. We obtained fourfold enrichment regardless of the tested samples, but with some variations according to the enriched regions. The accuracy of our assembly was further confirmed by PCR in the agrestis cultivar. We discussed parameters that could influence the enrichment and accuracy of NAS generated assemblies.</p><p><strong>Conclusions: </strong>Overall, we demonstrated that NAS is a simple and efficient approach for exploring complex genomic regions, such as clusters of Nucleotide-binding site leucine-rich repeat (NLR) resistance genes. These regions are characterized by containing a high number of copy number variations, presence-absence polymorphisms and repetitive elements. These features make accurate assembly challenging but are crucial to study due to their central role in plant immunity and disease resistance. This approach facilitates resistance gene characterization in a large number of individuals, as required when breeding new cultivars suitable for the agroecological transition.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"126"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390000","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}

{"title":"Epidermal growth factor dampens pro-inflammatory gene expression induced by interferon-gamma in global transcriptome analysis of keratinocytes.","authors":"David C Gibbs, Myles R McCrary, Carlos S Moreno, Lindsey Seldin, Chaoran Li, Nourine A H Kamili, Brian P Pollack","doi":"10.1186/s12864-025-11237-1","DOIUrl":"10.1186/s12864-025-11237-1","url":null,"abstract":"<p><strong>Background: </strong>Epidermal growth factor receptor inhibitors (EGFRIs) are used to treat certain cancers but frequently cause cutaneous inflammation that can hinder treatment. This is due in part to the effects of EGFRIs on pro-inflammatory signaling by interferon-γ (IFN-γ). However, the impact of EGFR ligands (i.e. EGF) on interferon signaling is unclear. The purpose of this study was to investigate the impact of EGF on IFN-γ transcriptional responses on a genome-wide scale in keratinocytes.</p><p><strong>Methods: </strong>RNA-seq was performed in human keratinocyte (HaCaT) cells treated with IFN-γ, EGF, both, or neither (control). Differentially expressed genes in each treatment group, relative to control, were identified using DESeq2 with a false discovery rate (FDR) threshold of 0.01. Associated biologic processes and gene pathways were examined in gene-set enrichment analyses. Correlations between gene expression were investigated in vivo using RNA-seq data from biopsies of psoriatic and matched normal skin, which were collected from 116 individuals with psoriasis enrolled in the AMAGINE randomized clinical trials.</p><p><strong>Results: </strong>Of the 2,792 differentially expressed genes following IFN-γ treatment, 2,083 (75%) were no longer differentially expressed when EGF was added. IFN-γ-induced genes with significantly lower expression in the presence of EGF included CXCL10, IL-6, IL-1 A, HLA-DMA, and GBP5 (activator of the NLRP3 inflammasome); the top enriched biologic processes and pathways were related to MHC-class II antigen presentation (GO:0019886) and cytokine signaling (KEGG:04060). Consistent with our in vitro findings, the expression of CXCL10 and GBP5, as well as the combined expression z-scores of genes in the enriched MHC-class II and cytokine signaling pathways, were significantly lower in skin biopsies with higher EGF expression compared to those with lower EGF expression among individuals with psoriasis.</p><p><strong>Conclusions: </strong>Our findings suggest that the pro-inflammatory IFN-γ-induced transcriptome may be globally attenuated by EGF in keratinocytes, supporting an immunomodulatory role of EGF in the skin. These studies provide insights for the non-canonical immunomodulatory role of EGF signaling and why blocking EGFR signaling (e.g., with EGFRIs) can cause cutaneous inflammation.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"122"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381458","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}

{"title":"Effects of a transient lack of dietary mineral phosphorus on renal gene expression and plasma metabolites in two high-yielding laying hen strains.","authors":"Hiba Qasir, Henry Reyer, Michael Oster, Siriluck Ponsuksili, Nares Trakooljul, Vera Sommerfeld, Markus Rodehutscord, Klaus Wimmers","doi":"10.1186/s12864-025-11294-6","DOIUrl":"10.1186/s12864-025-11294-6","url":null,"abstract":"<p><strong>Background: </strong>There is an emerging body of evidence that current poultry feed is formulated in excess for phosphorus (P), which results in unnecessarily high P excretions. Sustainable concepts for agricultural P flows should trigger animal-intrinsic mechanisms for efficient P utilization. In the current study, Lohmann Brown (LB) and Lohmann Selected Leghorn (LSL) laying hens were fed either a high P diet (P+) with 1 g/kg mineral P supplement or a low P diet (P-) with 0 g/kg mineral P supplement for a period of 4 weeks prior to sampling. Before and after onset of laying, i.e., at 19 and 24 weeks of life, kidney and plasma samples were collected to investigate the endogenous P utilization in response to restricted dietary P, laying hen strain, and sexual maturation.</p><p><strong>Results: </strong>Plasma analyses of minerals and metabolites confirmed the response to a low P diet, which was characterized by a significant reduction in plasma P levels at week 19 in both strains. The plasma calcium (Ca) levels were tightly regulated throughout the entire experimental period. Notably, there was a numerical trend of increased plasma calcitriol levels in P- fed birds of both strains compared to the P + group, which might have mediated a substantial role regarding the adaptive responses to low P supply. At week 19, RNA sequencing of kidney identified 1,114 and 556 differentially expressed genes (DEGs) unique to the LB and LSL strains, respectively. The number of DEGs declined with increasing maturity of the hens culminating in 90 and 146 DEGs for LB and LSL strains at week 24. Analyses revealed an enrichment of pathways related to energy metabolism and cell cycle, particularly at week 19 in both strains. The diet-specific expression of target genes involved in P homeostasis highlighted transcripts related to active (SLC34A1, SLC20A2) and passive mineral transport (CLDN14, CLDN16), Ca utilization (STC1, CALB1), and acid-base balance (CA2, SLC4A1).</p><p><strong>Conclusions: </strong>Results suggest that both laying hen strains adapted to the lack of mineral P supplements and achieved a physiological Ca: P-ratio in body compartments through endogenous regulation as evidenced via the endocrine profile.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"129"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389913","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}

{"title":"Genome-wide characterization of circular RNAs in three rat models of pulmonary hypertension reveals distinct pathological patterns.","authors":"Gaohui Fu, Lin Qiu, Jun Wang, Shujin Li, Jinglin Tian, Jiayu Wu, Xinyang Lin, Yiheng Zhu, Zixin Liu, Lingjie Luo, Ku Wang, Feilong Zhao, Jiahao Kuang, Shuangqing Liang, Shiran Liang, Yuqing Guo, Yuping Hong, Yonghao Yi, Jinyong Huang, Yanqin Niu, Kang Kang, Deming Gou","doi":"10.1186/s12864-025-11239-z","DOIUrl":"10.1186/s12864-025-11239-z","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a devastating disease marked by elevated pulmonary artery pressure, resulting in right ventricular (RV) failure and mortality. Despite the identification of several dysregulated genes in PH, the involvement of circular RNAs (circRNAs), a subset of long noncoding RNAs, remains largely unknown.</p><p><strong>Methods: </strong>In this study, high-throughput RNA sequencing was performed to analyze the genome-wide expression patterns of circRNAs in pulmonary arteries from three models of PH rats induced by hypoxia (Hyp), hypoxia/Sugen5416 (HySu), and monocrotaline (MCT). Differentially expressed circRNAs (DEcircRNAs) were identified, and a weighted gene coexpression network was constructed to explore circRNA networks associated with PH pathogenesis. A circRNA-miRNA-mRNA regulatory network was built, and the functional significance of targeted mRNAs was evaluated. Single-cell RNA sequencing provided insights into the distribution of cell type-specific circRNAs across PH progression.</p><p><strong>Results: </strong>Our analysis revealed 45 circRNAs exhibiting significant changes across all three PH rat models, with their host genes participating in the calcium signaling and muscle contraction. We identified 372 PH-related circRNA-miRNA-mRNA interactions, shedding light on the regulatory networks during PH development. Furthermore, we uncovered 186, 195 and 311 Hyp-, Hysu- and MCT-specific circRNAs, respectively. These circRNAs were enriched in distinct biological processes, emphasizing their unique regulatory roles. Single-cell spatial distribution analysis of these circRNAs in the pulmonary arteries of PH patients revealed that Hyp-specific circRNA predominantly appeared in the pulmonary vascular structural cells, while HySu- and MCT-specific circRNAs exhibited broader distribution, including significant enrichment in immune-related cells.</p><p><strong>Conclusion: </strong>Our study presents the first comprehensive view of circRNA regulatory networks in the pulmonary arteries of three PH rat models. We provide insights into PH-associated circRNAs, particularly their involvement in calcium signaling and muscle contraction.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"127"},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389956","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}