Functional & Integrative Genomics最新文献

{"title":"TFAP2A-regulated CRNDE enhances colon cancer progression and chemoresistance via RIPK3 interaction","authors":"Xin Gao,&nbsp;Yanming Huang,&nbsp;Tonghui Wei,&nbsp;Jingmin Xue,&nbsp;Filippov Iurii,&nbsp;Laishou Yang,&nbsp;Liying Wang,&nbsp;Hao Li,&nbsp;Genshen Mo,&nbsp;Yuze Huang,&nbsp;Haonan Xie,&nbsp;Hang Wang,&nbsp;Shenghan Lou,&nbsp;Peng Han","doi":"10.1007/s10142-025-01545-w","DOIUrl":"10.1007/s10142-025-01545-w","url":null,"abstract":"<div><p>Colon cancer (CC) is a common malignancy with rising incidence worldwide. Despite advances in treatment strategies, many patients still face a poor prognosis due to the development of drug resistance. Long non-coding RNAs (lncRNAs) have emerged as important regulators of various biological processes and have been implicated in cancer progression. Among them, colorectal neoplasia differentially expressed (CRNDE) has drawn attention for its potential roles in different cancers. However, its specific functions in CC remain unclear. In this study, we identified CRNDE as highly expressed in CC, contributing to tumor progression and drug resistance. Mechanically, CRNDE is regulated by the transcription factor TFAP2A. Additionally, CRNDE inhibits pyroptosis, a form of programmed cell death, by promoting the ubiquitin-mediated degradation of RIPK3, thereby reducing the sensitivity of CC cells to 5-fluorouracil (5-FU). Our findings suggest that the TFAP2A/CRNDE/RIPK3 axis plays critical roles in colon cancer progression and chemoresistance, highlighting potential therapeutic targets for improving treatment outcomes.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01545-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423314","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":"Deciphering nutrient stress in plants: integrative insight from metabolomics and proteomics","authors":"Abiodun Yusuff Moshood,&nbsp;Mukhtar Iderawumi Abdulraheem,&nbsp;Linze Li,&nbsp;Yanyan Zhang,&nbsp;Vijaya Raghavan,&nbsp;Jiandong Hu","doi":"10.1007/s10142-025-01551-y","DOIUrl":"10.1007/s10142-025-01551-y","url":null,"abstract":"<div><p>To comprehend the responses and resilience of plants under unfavorable environmental conditions, it is crucial to study the metabolomics and proteomic insights into nutrient stress. Nutrient stress substantially challenges agriculture, impacting plant growth, development, and productivity due to a lack or imbalance of essential nutrients, which can happen due to poor soil quality, limited nutrient availability, or unfavorable climatic conditions. Although there has been significant progress in the study of plant nutrient stress using metabolomics and proteomics, several challenges and research gaps still need to be addressed, such as the standardized experimental protocols, data integration strategies, and bioinformatic tools are necessary for comparative analysis and interpretation of omics data. Hence, this review explores the theoretical frameworks of metabolomics and proteomics as powerful tools to decode plant responses to nutrient stress, addressing critical knowledge gaps in the field. This review highlights the advantages of integrative analyses, combining metabolomics, proteomics, and transcriptomics, to uncover the molecular networks governing nutrient stress resilience. Key findings underscore the potential of these techniques to enhance breeding strategies and genetic engineering efforts aimed at developing nutrient-efficient crops. Through metabolomics and proteomic analyses, novel molecular components and regulatory networks have been revealed as responsive to nutrient stress, and this breakthrough has the potential to bolster plant resilience and optimize nutrient utilization. Understanding the synergistic roles of metabolites and proteins in nutrient stress resilience has profound implications for crop improvement and agricultural sustainability. Future research should focus on refining integrative methodologies and exploring their applications across diverse plant species and environmental conditions, paving the way for innovative solutions to nutrient stress challenges. </p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423254","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":"Characterization of 4-coumarate CoA ligase (4CL) gene family and functional study of Sm4CL2/3/7/9 in Salvia miltiorrhiza","authors":"Fan Fu,&nbsp;Huiting Qin,&nbsp;Yujie Xin,&nbsp;Qianmo Li,&nbsp;Heng Kang,&nbsp;Limin Han,&nbsp;Wenping Hua,&nbsp;Xiaoyan Cao","doi":"10.1007/s10142-025-01541-0","DOIUrl":"10.1007/s10142-025-01541-0","url":null,"abstract":"<div><p>The 4-coumarate CoA ligase (4CL, EC6.2.1.12) enzyme is pivotal for the final step of three shared stages in the general phenylpropane metabolic pathway, which plays a critical role in the biosynthesis of a diverse array of metabolites (e.g., phenolic acids, flavonoids, lignin, anthocyanins, and coumarins). Ten <i>4CL</i> genes have been identified in the genome of <i>Salvia miltiorrhiza</i> (a model medicinal plant), the majority of these genes have not yet been characterized. In this study, the expression profiles of the <i>Sm4CLs</i> gene family were analyzed by qRT-PCR. Among the ten members, <i>Sm4CL7</i> had the highest expression across various tissues, while <i>Sm4CL5</i> showed the lowest transcription levels. Notably, <i>Sm4CL2/3/4/6/7/9/10</i> were significantly responsive to methyl jasmonate (MeJA) treatments. Ten <i>4CLs</i> were divided into four groups via phylogenetic analysis, while <i>Sm4CL2/3/7/9</i> that represented each group were selected for further investigation. The GUS staining results of <i>proSm4CL2/3/7/9::GUS</i> transgenic <i>Arabidopsis thaliana</i> were strongly consistent with the qRT-PCR results, and all four <i>Sm4CLs</i> were located in the cytoplasm. Compared with the control, transgenic <i>S. miltiorrhiza</i> plants that overexpressed <i>Sm4CL2/3/7/9</i> possessed reduced contents of p-coumaric acid and caffeic acid, albeit higher levels of rosmarinic acid and salvianolic acid. In conclusion, this research expands our understanding of the <i>Sm4CL</i> gene family and offers insights into enhancing the quality of <i>S. miltiorrhiza</i> and the production of secondary metabolites through the targeted manipulation of 4CL enzymes.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373271","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":"Comprehensive insights and In silico analysis into the emerging role of LincRNAs in lung diseases pathogenesis; a step toward ncRNA precision","authors":"Nadia M. Hamdy,&nbsp;Mohamed Bakr Zaki,&nbsp;Nourhan M. Abdelmaksoud,&nbsp;Shereen Saeid Elshaer,&nbsp;Mai A. Abd-Elmawla,&nbsp;Nehal I. Rizk,&nbsp;Doaa Fathi,&nbsp;Ahmed S. Doghish,&nbsp;Ahmed I. Abulsoud","doi":"10.1007/s10142-025-01540-1","DOIUrl":"10.1007/s10142-025-01540-1","url":null,"abstract":"<div><p>Long non-coding RNAs (lncRNAs) have emerged as essential regulators of gene expression, significantly influencing various biological processes. Approximately half of all lncRNAs are classified as long intergenic non-coding RNAs (lincRNAs), which are situated among coding genes. Recent studies have documented the role of lincRNAs in the pathogenesis of lung diseases, including lung cancer, pulmonary fibrosis, and pulmonary arterial hypertension. These lincRNAs can modulate gene expression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional regulation. By functioning as competing endogenous RNAs (ceRNAs), lincRNAs can affect the activity of microRNAs (miRNAs) and their corresponding target genes. This review delves into the intricate mechanisms by which lincRNAs contribute to the development and progression of various lung diseases. Furthermore, it discusses the potential of lincRNAs as therapeutic targets.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01540-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254319","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":"miRNAs and their multifaceted role in cutaneous wound healing","authors":"Reda M. Mansour,&nbsp;Sherif S. Abdel Mageed,&nbsp;Farah A. Awad,&nbsp;Mohamed M. Sadek,&nbsp;Shehab Ahmed Adel,&nbsp;Alaa Ashraf,&nbsp;Khaled M. Alam-Eldein,&nbsp;Nada E. Ahmed,&nbsp;Rana Y. Abdelaziz,&nbsp;Esraa Farid Tolba,&nbsp;Hend H. Mohamed,&nbsp;Nehal I. Rizk,&nbsp;Mohamed O. Mohamed,&nbsp;Osama A. Mohammed,&nbsp;Ahmed S. Doghish","doi":"10.1007/s10142-025-01535-y","DOIUrl":"10.1007/s10142-025-01535-y","url":null,"abstract":"<div><p>The dynamic, complex process of cutaneous wound healing is required to restore skin integrity following an injury. This intricate process consists of four sequential and overlapping phases: hemostasis, inflammation, proliferation, and remodeling. Hemostasis immediately begins to function in response to vascular injury, forming a clot that stops the bleeding. To fight infection and remove debris, immune cells are enlisted during the inflammatory phase. Angiogenesis, re-epithelialization, and the creation of new tissue are all components of proliferation, whereas tissue maturation and scarring are the outcomes of remodeling. Chronic wounds, like those found in diabetic ulcers, frequently stay in a state of chronic inflammation because they are unable to go through these stages in a coordinated manner. The important regulatory roles that microRNAs (miRNAs) play in both normal and pathological wound healing have been highlighted by recent investigations. The miRNAs, small non-coding RNAs, modulate gene expression post-transcriptionally, profoundly impacting cellular functions. During the inflammatory phase, miRNAs control pro- and anti-inflammatory cytokines, as well as the activity of immune cells such as neutrophils and macrophages. Additionally, miRNAs are essential components of signaling networks related to inflammation, such as the toll-like receptor (TLR), nuclear factor kappa B (NF-kB), and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways. Some miRNAs have been discovered to either increase or alleviate inflammatory reactions, indicating their potential as therapeutic targets. Other miRNAs aid in angiogenesis by promoting the development of new blood vessels, which are essential for providing oxygen and nutrients to the healing tissue. They also affect keratinocyte migration and proliferation during the re-epithelialization phase, which involves growing new epithelial cells over the lesion. Another function of miRNAs is that they control the deposition of extracellular matrix (ECM) and the creation of scars during the remodeling phase. The abnormal expression of miRNAs in chronic wounds has led to the exploration of miRNA-based treatments. With a focus on resistant instances such as diabetic wounds, these therapeutic techniques seek to improve wound healing results by correcting the dysregulated miRNA expression.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143108052","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":"Advancing vegetable genetics with gene editing: a pathway to food security and nutritional resilience in climate-shifted environments","authors":"Rajib Roychowdhury,&nbsp;Soumya Prakash Das,&nbsp;Siddhartha Das,&nbsp;Sabarni Biswas,&nbsp;Manish Kumar Patel,&nbsp;Ajay Kumar,&nbsp;Umakanta Sarker,&nbsp;Sikander Pal Choudhary,&nbsp;Ranjan Das,&nbsp;Kalenahalli Yogendra,&nbsp;Sunil S Gangurde","doi":"10.1007/s10142-025-01533-0","DOIUrl":"10.1007/s10142-025-01533-0","url":null,"abstract":"<div><p>As global populations grow and climate change increasingly disrupts agricultural systems, ensuring food security and nutritional resilience has become a critical challenge. In addition to grains and legumes, vegetables are very important for both human and animals because they contain vitamins, minerals, and fibre. Enhancing the ability of vegetables to withstand climate change threats is essential; however, traditional breeding methods face challenges due to the complexity of the genomic clonal multiplication process. In the postgenomic era, gene editing (GE) has emerged as a powerful tool for improving vegetables. GE can help to increase traits such as abiotic stress tolerance, herbicide tolerance, and disease resistance; improve agricultural productivity; and improve nutritional content and shelf-life by fine-tuning key genes. GE technologies such as Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR-Cas9) have revolutionized vegetable breeding by enabling specific gene modifications in the genome. This review highlights recent advances in CRISPR-mediated editing across various vegetable species, highlighting successful modifications that increase their resilience to climatic stressors. Additionally, it explores the potential of GE to address malnutrition by increasing the nutrient content of vegetable crops, thereby contributing to public health and food system sustainability. Additionally, it addresses the implementation of GE-guided breeding strategies in agriculture, considering regulatory, ethical, and public acceptance issues. Enhancing vegetable genetics via GE may provide a reliable and nutritious food supply for an expanding global population under more unpredictable environmental circumstances.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073230","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":"The role of exosomal non-coding RNAs in the breast cancer tumor microenvironment","authors":"Mohamed J. Saadh,&nbsp;Omer Qutaiba B. Allela,&nbsp;Radhwan Abdul Kareem,&nbsp;Suhas Ballal,&nbsp;Mamata Chahar,&nbsp;Suman Saini,&nbsp;G. V. Siva Prasad,&nbsp;Hayder Naji Sameer,&nbsp;Atheer Khdyair Hamad,&nbsp;Zainab H. Athab,&nbsp;Mohaned Adil","doi":"10.1007/s10142-025-01531-2","DOIUrl":"10.1007/s10142-025-01531-2","url":null,"abstract":"<div><p>The leading form of cancer affecting females globally is breast cancer, characterized by an unregulated growth of cells within the breast. Therefore, examining breast tissue is crucial in accurately identifying and treating this disease. Exosomes are very small enclosures bounded by a layer of cells and produced by a variety of cells present in the cancerous tissue surroundings. They play a crucial role in several biological functions in cancerous tumors. These exosomes carry non-coding RNAs (ncRNAs) and are discharged into the TME, where they are instrumental in the development and advancement of tumors. Additionally, the ncRNAs enclosed in exosomes act as significant mediators of communication within cells. Consequently, there is limited comprehension regarding the precise roles and targets of exosomal RNA in regulation, as research in this area is still in its preliminary phases. This piece provides a comprehensive overview of the latest studies on exosomes, delving into their impact on the behavior of cancer cells and immune cells. Moreover, it presents a compilation of the diverse forms of non-coding RNA molecules found in exosomes released by both cancerous and supportive cells, including circular RNAs, microRNAs, and long non-coding RNAs. Current research has proven the noteworthy influence that non-coding RNA molecules have on the progression, proliferation, drug resistance, and immune responses of breast cancer cells.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073279","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":"From fatty liver to fibrosis: the impact of miRNAs on NAFLD and NASH","authors":"Reda M. Mansour,&nbsp;Sherif S. Abdel Mageed,&nbsp;Ahmed I. Abulsoud,&nbsp;Ghadir A Sayed,&nbsp;Radwa H. Lutfy,&nbsp;Farah A. Awad,&nbsp;Mohamed M. Sadek,&nbsp;Abanoub A. S. Shaker,&nbsp;Osama A. Mohammed,&nbsp;Mustafa Ahmed Abdel-Reheim,&nbsp;Hanan Elimam,&nbsp;Ahmed S. Doghish","doi":"10.1007/s10142-025-01544-x","DOIUrl":"10.1007/s10142-025-01544-x","url":null,"abstract":"<div><p>Non-alcoholic fatty liver disease (NAFLD) is a disease with various levels varying from fatty liver steatosis to acute steatosis which is non-alcoholic steatohepatitis (NASH), which can develop into hepatic failure, as well as in some conditions it can develop into hepatocellular carcinoma (HCC). In the NAFLD and NASH context, aberrant microRNA (miRNA) expression has a thorough contribution to the incidence and development of these liver disorders by influencing key biological actions, involving lipid metabolism, inflammation, and fibrosis. Dysregulated miRNAs can disrupt the balance between lipid accumulation and clearance, exacerbate inflammatory responses, and promote fibrogenesis, thus advancing the severeness of the disorder from simple steatosis to more complex NASH. In the current review, the latest development concerned with the activity of complex regulatory networks of miRNA in the incidence as well as the evolution of NAFLD is to be discussed, also conferring about the miRNAs’ role in the onset, pathogenesis as well as diagnosis of NAFLD and NASH discussing miRNAs’ role as diagnostic biomarkers and their therapeutic effects on NAFLD/NASH.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063069","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":"Gonadal miRNomes and transcriptomes in infected fish reveal sexually dimorphic patterns of the immune response","authors":"Tosca A. van Gelderen,&nbsp;Pinky Debnath,&nbsp;Silvia Joly,&nbsp;Edgar Bertomeu,&nbsp;Neil Duncan,&nbsp;Dolors Furones,&nbsp;Laia Ribas","doi":"10.1007/s10142-025-01537-w","DOIUrl":"10.1007/s10142-025-01537-w","url":null,"abstract":"<div><p>Fish disease outbreaks caused by bacterial burdens are responsible for decreasing productivity in aquaculture. Unraveling the molecular mechanisms activated in the gonads after infections is pivotal for enhancing husbandry techniques in fish farms, ensuring disease management, and selecting the most resilience phenotype. The present study, with an important commercial species the European sea bass (<i>Dicentrarchus labrax</i>), an important commercial species in Europe, examined changes in the miRNome and transcriptome 48 h after an intraperitoneal infection with <i>Vibrio anguillarum</i>. The findings indicate that following infection, testes exhibited more pronounced alterations in both the miRNome and transcriptome. Specifically, males showed approximately 26% more differentially expressed genes in testicular genes compared to females (2,624 vs. 101 DEGs). Additionally, four miRNAs (miR-183-5p, miR-191-3p, miR-451-5p, and miR-724-5p) were significantly expressed post-infection in males, while none were identified in females. Interestingly, upon deep analysis of sexual dimorphic gene modules, a larger number of miRNAs were identified in infected females targeting genes related to the immune system compared to infected males. These results suggest that fish ovaries demonstrate greater resilience in response to infections by suppressing genes related to the immune system through a post-transcriptional mechanism performed by miRNAs. In contrast, testes activate genes related to the immune system and repress genes related to cellular processes to cope with the infection. In particular, the crosstalk between the miRNome and transcriptome in infected males revealed a pivotal gene, namely, insulin-like growth factor binding protein (<i>igfbp</i>), acting as a gene network hub in which miR-192-3p was connected. The current study elucidated the need to comprehend the basic immune regulatory responses associated with miRNAs and gene regulation networks that depend on fish sex. The data reveal the importance of considering sex as a factor in interpreting the immune system in fish to generate efficient protocols to prevent outbreaks in fish farms.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063071","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":"Leptin drives glucose metabolism to promote cardiac protection via OPA1-mediated HDAC5 translocation and Glut4 transcription","authors":"Fan Yang,&nbsp;Youfu He,&nbsp;Ling Zhao,&nbsp;Jing Huang,&nbsp;Fawang Du,&nbsp;Shui Tian,&nbsp;Yang Zhang,&nbsp;Xinghui Liu,&nbsp;Baolin Chen,&nbsp;Junhua Ge,&nbsp;Zhi Jiang","doi":"10.1007/s10142-024-01515-8","DOIUrl":"10.1007/s10142-024-01515-8","url":null,"abstract":"<div><p>Metabolic reprogramming, the shifting from fatty acid oxidation to glucose utilization, improves cardiac function as heart failure (HF) progresses. Leptin plays an essential role in regulating glucose metabolism. However, the crosstalk between leptin and metabolic reprogramming is poorly understood. We tested the hypothesis that leptin improves cardiac function after myocardial infarction via enhancing glucose metabolism. In the isoproterenol (ISO)-induced heart failure model in vitro, H9c2 cell apoptosis was assessed by the TUNEL and Annexin V/PI staining assay. Leptin-mediated mitochondrial fusion was performed via TEM, and glucose oxidation was explored, as well as the ECAR, OCR, and protein expression of the vital metabolic enzymes. By blocking OPA1 expression or HDAC5 inhibition, the mitochondrial dynamic and glucose metabolic were detected to evaluate the role of OPA1 and HDAC5 in leptin-stimulated glucose metabolism. In the mouse model of HF in vivo, intraperitoneal leptin administration appreciably increased glucose oxidation and preserved cardiac function 56 days after coronary artery ligation. In vitro, we identified the OPA1-dependent HDAC5 nucleus export as a crucial process in boosting glucose utilization by activating MEF2 to upregulate Glut4 expression using the RNA interference technique in H9c2 cells. In vivo, leptin promotes glucose utilization and confers heart functional and survival benefits in chronic ischemic HF. The current study provided a novel insight into the role of leptin in metabolic reprogramming and revealed potential therapeutic targets for chronic HF.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057702","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}