Functional & Integrative Genomics最新文献

{"title":"Application of a high-throughput swarm-based deep neural network Algorithm reveals SPAG5 downregulation as a potential therapeutic target in adult AML","authors":"Chinyere I Ajonu,&nbsp;Robert I Grundy,&nbsp;Graham R Ball,&nbsp;Dimitrios Zafeiris","doi":"10.1007/s10142-024-01514-9","DOIUrl":"10.1007/s10142-024-01514-9","url":null,"abstract":"<div><p>Gene‒gene interactions play pivotal roles in disease pathogenesis and are fundamental in the development of targeted therapeutics, particularly through the elucidation of oncogenic gene drivers in cancer. The systematic analysis of pathways and gene interactions is critical in the drug discovery process for various cancer subtypes. SPAG5, known for its role in spindle formation during cell division, has been identified as an oncogene in several cancers, although its specific impact on AML remains underexplored. This study leverages a high-throughput swarm-based deep neural network (SDNN) and transcriptomic data—an approach that enhances predictive accuracy and robustness through collective intelligence—to augment, model, and enhance the understanding of the TP53 pathway in AML cohorts. Our integrative systems biology approach identified SPAG5 as a uniquely downregulated driver in adult AML, underscoring its potential as a novel therapeutic target. The interaction of SPAG5 with key hub genes such as MDM2 and CDK1 not only reinforces its role in tumour suppression through negative regulation but also highlights its potential in moderating the phenotypic and genomic alterations associated with AML progression. This study of the role and interaction dynamics of SPAG5 sets the stage for future research aimed at developing targeted and personalized treatment approaches for AML, utilizing the capabilities of genetic interventions.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-024-01514-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142938931","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":"A cutting-edge investigation of the multifaceted role of SOX family genes in cancer pathogenesis through the modulation of various signaling pathways","authors":"Saade Abdalkareem Jasim,&nbsp;Shireen Hamid Farhan,&nbsp;Irfan Ahmad,&nbsp;Ahmed Hjazi,&nbsp;Ashwani Kumar,&nbsp;Mohammed Abed Jawad,&nbsp;Atreyi Pramanik,&nbsp;M. A. Farag Altalbawy,&nbsp;Salim B. Alsaadi,&nbsp;Munther Kadhim Abosaoda","doi":"10.1007/s10142-024-01517-6","DOIUrl":"10.1007/s10142-024-01517-6","url":null,"abstract":"<div><p>This detailed study examines the complex role of the SOX family in various tumorigenic contexts, offering insights into how these transcription factors function in cancer. As the study progresses, it explores the specific contributions of each SOX family member. The significant roles of the SOX family in the oncogenic environment are well-recognized, highlighting a range of regulatory mechanisms that influence tumor progression. In brain, lung, and colorectal cancers, SOX types like SOX2, SOX3, and SOX4 promote the migration, proliferation, and angiogenesis of cancer cells. Conversely, in pancreatic, gastric, and breast cancers, SOX types, including SOX1, SOX9, and SOX17 inhibit various cancer cell activities such as proliferation and invasion. This thorough investigation enhances our understanding of the SOX family’s complex role in cancer, establishing a foundation for future research and potential therapeutic strategies targeting these versatile transcription factors.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925589","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":"Towards assembling functional cyanobacterial β-carboxysomes in Oryza sativa chloroplasts","authors":"Gurbir Kaur Sidhu,&nbsp;Rakesh Pandey,&nbsp;Gurdeep Kaur,&nbsp;Anjulata Singh,&nbsp;Sangram K. Lenka,&nbsp;Pallavolu M. Reddy","doi":"10.1007/s10142-024-01518-5","DOIUrl":"10.1007/s10142-024-01518-5","url":null,"abstract":"<div><p>The major limiting factor of photosynthesis in C3 plants is the enzyme, rubisco which inadequately distinguishes between carbon dioxide and oxygen. To overcome catalytic deficiencies of Rubisco, cyanobacteria utilize advanced protein microcompartments, called the carboxysomes which envelopes the enzymes, Rubisco and Carbonic Anhydrase (CA). These microcompartments facilitate the diffusion of bicarbonate ions which are converted to CO₂ by CA, following in an increase in carbon flux near Rubisco boosting CO₂ fixation process. Inspired by this mechanism, our study aims to improve photosynthetic efficiency in the C₃ model crop, rice (<i>Oryza sativa</i>), by stably engineering the genetic components of the β-carboxysome of <i>Synechococcus elongatus</i> PCC 7942 (hereafter, Syn7942) in the rice genome. We demonstrated this proof of concept by developing two types of transgenic rice plants. The first type involved targeting the chloroplasts with three key carboxysome structural proteins (<i>ccmL</i>, <i>ccmO</i>, and <i>ccmK</i>) and a chimeric protein (<i>ccmC</i>), which integrates domains from four distinct carboxysome proteins. The second type combined these proteins with the introduction of cyanobacterial Rubisco targeted to chloroplasts. Additionally, in the second transgenic background, RNA interference was employed to silence the endogenous rice Rubisco along with stromal carbonic anhydrase gene. The transgenic plants exhibited the assembly of carboxysome-like compartments and aggregated proteins in the chloroplasts and the second type demonstrated reduced plant growth and yield. We have followed a bottom-up approach for targeting the cyanobacterial CCM in rice chloroplast which would help in stacking up the components further required for increasing the photosynthetic efficiency in future.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912916","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":"Circular RNAs in the pathogenesis of SARS-CoV-2: potential diagnostic biomarkers and therapeutic targets","authors":"JiaJie Wu,&nbsp;Lele Li,&nbsp;Wei Xu,&nbsp;Xiaoping Xia,&nbsp;Yingping Wu","doi":"10.1007/s10142-024-01509-6","DOIUrl":"10.1007/s10142-024-01509-6","url":null,"abstract":"<div><p>Since December 2019, the global dissemination of a novel coronavirus has precipitated a notable public health crisis, prompting considerable interest and scrutiny from governmental and scholarly entities. Substantial research efforts have been dedicated to exploring diverse facets of this novel coronavirus, encompassing its pathogenesis, transmission dynamics, and therapeutic interventions. Recent findings suggest that circular RNAs (circRNAs) exert a pivotal influence on modulating viral infectivity and immune defense mechanisms. The detection of differentially expressed circRNAs in individuals afflicted with SARS-CoV-2 signifies a noteworthy advancement in understanding the molecular mechanisms underpinning viral pathogenesis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912999","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":"Unraveling the organellar genomic landscape of the therapeutic and entheogenic plant Mimosa tenuiflora: insights into genetic, structural, and evolutionary dynamics","authors":"Vitor Trinca,&nbsp;Saura R. Silva,&nbsp;João V. A. Almeida,&nbsp;Vitor F. O. Miranda,&nbsp;José V. Costa-Macedo,&nbsp;Tatiane K. B. A. Carnaval,&nbsp;Draulio B. Araújo,&nbsp;Francisco Prosdocimi,&nbsp;Alessandro M. Varani","doi":"10.1007/s10142-024-01511-y","DOIUrl":"10.1007/s10142-024-01511-y","url":null,"abstract":"<div><p><i>Mimosa tenuiflora</i>, popularly known as “Jurema-Preta”, is a perennial tree or shrub native to the tropical regions of the Americas, particularly among Afro-Brazilian and Indigenous Brazilian communities. Known for producing N,N-Dimethyltryptamine, a psychedelic compound with profound psychological effects, Jurema-Preta has been studied for its therapeutic potential in mental health. This study offers a comprehensive analysis of the plastid (ptDNA) and mitochondrion (mtDNA) genomes of <i>M. tenuiflora</i>. The 165,639 bp ptDNA sequence features the classical quadripartite structure with 130 protein-coding genes. Comparative genomics among <i>Mimosa</i> species shows high sequence identity in protein-coding genes, with variation in the <i>rpoC1</i>, <i>clpP</i>, <i>ndhA</i>, and <i>ycf1</i> genes. The ptDNA junctions display distinct features, such as the deletion of the <i>rpl22</i> gene, and specific simple sequence repeats highlight genetic variation and unique motifs as valuable genetic markers for population studies. Phylogenetic analysis places <i>M. tenuiflora</i> in the Caesalpinioideae, closely related to <i>M. pigra</i> and <i>M. pudica</i>. The 617,839 bp mtDNA sequence exhibits a complex structure with multiple genomic arrangements due to large repeats, encoding 107 protein-coding genes, including the ptDNA <i>petG</i> and <i>psaA</i> genes, and non-retroviral RNA mitoviruses sequences. Comparative analysis across Fabaceae species reveals limited conservation, emphasizing the dynamic nature of plant mitochondrial genomes. The genomic characterization of <i>M. tenuiflora</i> enhances understanding of its evolutionary dynamics, providing insights for population studies and potential applications in ethnopharmacology and conservation.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905987","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":"Barley stripe mosaic virus-induced gene silencing for functional validation of abiotic stress in barley","authors":"Tayachew Admas,&nbsp;Maru Wudu,&nbsp;Hailu Berhanie","doi":"10.1007/s10142-024-01508-7","DOIUrl":"10.1007/s10142-024-01508-7","url":null,"abstract":"<div><p>The <i>barley stripe mosaic virus</i> (<i>BSMV</i>) uses its genomic RNA components (alpha, beta, and gamma) as an efficient method for studying gene functions. It is a newly developed method that utilizes gene transcript suppression to determine the role of plant genes. <i>BSMV</i> derived from virus induced gene silencing (VIGS) is capable of infecting various key farming crops like barley, wheat, rice, corn, and oats. Nevertheless, the growing acceptance and enhancement of <i>BSMV</i>-VIGS will benefit all kinds of plants. Abiotic stresses such as drought and salt are highly affecting plant growth, development, and production. <i>BSMV</i>-induced temporal gene knockdown is performed during particular stressful situations to determine their specific function. The quick physiological and biochemical changes aid in confirming the role of the target genes. VIGS has a significant role to improve crop genetics and breeding, despite having certain restrictions. Thus, exploring the possible solution and addressing these difficulties will enhance the technology in the continuous advancement of plant manufacturing. <i>BSMV</i>-mediated VIGS has become popular in functional genomics; gene function can be determined without permanent transformation. In general, <i>BSMV</i>-mediated VIGS will be very helpful in the ongoing effort to develop resilient crops.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142889562","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":"Xuanhong Dingchuan Tang suppresses bronchial asthma inflammation via the microRNA-107-3p/PTGS2/MAPK axis","authors":"Xi Ming,&nbsp;Yingzhu Lu,&nbsp;Huihui Huang,&nbsp;Jialin Zheng,&nbsp;Tianzi Wang,&nbsp;Zhuoqun Li,&nbsp;Xingzhu Yu,&nbsp;Lei Xiong","doi":"10.1007/s10142-024-01506-9","DOIUrl":"10.1007/s10142-024-01506-9","url":null,"abstract":"<div><p>This study aimed to investigate the mechanism of Xuanhong Dingchuan Tang (XHDCT) in delaying bronchial asthma inflammation via the microRNA (miR)-107-3p/prostaglandin endoperoxide synthase 2 (PTGS2)/mitogen-activated protein kinase (MAPK) axis. Based on the network pharmacological analysis, XHDCT chemical constituents and targets of each chemical constituent were screened through the TCMSP database, and differential-expressed genes of bronchial asthma were obtained from the GEO database, which were intersected to get XHDCT potential anti-inflammatory targets. The key anti-inflammatory targets of XHDCT were acquired by protein-protein interaction (PPI) analysis of the candidate targets. Bronchial asthma mouse models were established and the pathological changes of lung tissues were observed. Serum IgE levels were tested. Total cells and eosinophils in bronchoalveolar lavage fluid (BALF) were counted. The expression of Th2-associated cytokines (interleukin (IL)-4, IL-5, and IL-13) and chemokines (monocyte chemoattractant protein-1 (MCP-1) and eotaxin) in BALF were measured. The targeting relationship between miR-107-3p and PTGS2 was tested. XHDCT delayed bronchial asthma inflammation in in-vivo asthma mouse models. A total of 155 active ingredients and their 341 targets were intersected with bronchial asthma-relevant genes, obtaining 20 potential targets of XHDCT for bronchial asthma treatment. Based on the PPI and “drug-component-target” network diagram, PTGS2 was found to be in a central position. PTGS2 was downregulated and miR-107-3p was upregulated in bronchial asthma mice after XHDCT treatment. PTGS2 overexpression activated the MAPK signaling pathway to promote inflammation in bronchial asthma mice, whereas inflammatory symptoms were reduced and the MAPK signaling pathway was inhibited after XHDCT treatment. miR-107-3p was an upstream regulatory miRNA for PTGS2. After miR-107-3p interference, the activation of the PTGS2/MAPK axis promoted inflammation in bronchial asthma mice, whereas the inflammatory symptoms were reduced after XHDCT treatment. XHDCT promotes anti-inflammatory effects in bronchial asthma via the miR-107-3p/PTGS2/MAPK axis.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142859698","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: Decoding the role of durum wheat ascorbate peroxidase TdAPX7B-2 in abiotic stress response","authors":"Kaouthar Feki,&nbsp;Sana Tounsi,&nbsp;Hanen Kamoun,&nbsp;Abdulrahman Al-Hashimi,&nbsp;Faiçal Brini","doi":"10.1007/s10142-024-01507-8","DOIUrl":"10.1007/s10142-024-01507-8","url":null,"abstract":"","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142810846","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":"Integration of osimertinib-targeted EGFR gene-associated differential gene expression in constructing a prognostic model for lung adenocarcinoma","authors":"Haiwen Li,&nbsp;Li Yang,&nbsp;Quan Yang,&nbsp;Zhu Liang,&nbsp;Wenmei Su,&nbsp;Lili Yu","doi":"10.1007/s10142-024-01499-5","DOIUrl":"10.1007/s10142-024-01499-5","url":null,"abstract":"<div><p>Lung adenocarcinoma (LUAD) is one of the deadliest cancers. Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy is an important approach for treating LUAD. However, the development of acquired resistance poses a serious clinical challenge. Our objective was to explore the differentially expressed genes (DEGs) associated with EGFR and detect biomarkers for diagnosing and treating osimertinib resistance in LUAD patients. LUAD datasets were downloaded from public databases. Differential expression analysis was performed to screen DEGs, and prognostic modules were constructed by Cox regression. Enrichment analysis, gene regulatory network analysis and immune microenvironment analysis were employed to explore the underlying mechanisms in LUAD. Finally, the expression of prognosis module genes (PMGs) was validated in 8 LUAD tissue specimens and 5 cell lines by qRT-PCR. In total, 13 differential module genes (<i>BIRC3, CCT6A, CPLX2, GLCCI1, GSTA1, HLA-DQB2, ID1, KCTD12, MUC15, NOTUM, NT5E, TCIM, and TM4SF4</i>) were screened for the construction of a prognostic module. Notably, <i>CCT6A</i> and <i>KCTD12</i> demonstrated excellent accuracy in the diagnosis of LUAD. Immune dysregulation and <i>BIRC3, HLA-DQB2, KCTD12</i>, and <i>NT5E</i> expression were significantly associated with invasive immune cells in LUAD patients. The expression level of <i>CCT6A</i> was highest in PC9-OR and H1975-OR cells, while the expression level of <i>KCTD12</i> was highest in paracancerous tissue and HBE cells. The constructed prognostic model showed promise in predicting the survival of LUAD patients. Notably, <i>KCTD12</i> and <i>CCT6A</i> might be candidate biomarkers for improving diagnostic performance and guiding individualized therapy for EGFR-TKI-resistant LUAD patients.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-024-01499-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798423","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":"Serine related gene CCT6A promotes metastasis of hepatocellular carcinoma via interacting with RPS3","authors":"Hongwei Cui,&nbsp;Li Jiang,&nbsp;Yujiao Zhou,&nbsp;You Zhou,&nbsp;Fan Li,&nbsp;Zhenzhen Zhang","doi":"10.1007/s10142-024-01497-7","DOIUrl":"10.1007/s10142-024-01497-7","url":null,"abstract":"<div><p>Metastasis is responsible for approximately 90% of lethality from solid tumors. Metabolic abnormalities are one of the key characteristics of tumor cells, closely associated with tumorigenesis and progression. The de novo synthesis pathway of serine is a key metabolic bypass in glycolysis, which could provide material and energy basis for the rapid proliferation of tumor cells by mediating one-carbon metabolism. The transformation of metabolic patterns is particularly pronounced in HCC, often leading to a high dependence of HCC cells on glycolysis. However, up to now, the underlying relationship between serine metabolism and HCC metastasis remains largely unknown. Through a series of bioinformatics methods, we reported CCT6A, a serine related gene, was particularly associated with metastatic events of HCC. We furtherly demonstrated that CCT6A was highly expressed in HCC cells with high metastatic potential. Gain- and loss-of-function analyses showed that CCT6A could promote HCC cells migration and invasion. Mechanistically, CCT6A was found to be interacted with RPS3, and might potentiate the metastasis of HCC by affecting some metabolic processes. Totally, our results suggest that the metabolic reprogramming induced by interacting between CCT6A and RPS3 could advance HCC metastasis, making the CCT6A/RPS3 axis a promising target for therapeutic intervention.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"24 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142761810","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}