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{"title":"Transcriptional dynamics and tissue-specific expression patterns of transposable elements in orthopteran insects","authors":"Muhammad Majid,&nbsp;Xuanzeng Liu,&nbsp;Hashim Khan,&nbsp;Yuan Huang","doi":"10.1016/j.gene.2024.149090","DOIUrl":"10.1016/j.gene.2024.149090","url":null,"abstract":"<div><div>Transposable elements (TEs) are prevalent in the genomes of orthopteran insects, contributing significantly to their genome evolution and diversity. In light of the existing gap in our understanding of TEs transcript dynamics in orthopteran insects, we recognize the critical need to undertake comprehensive analyses in this area. Therefore, we have decided to delve into the characterization of TE transcripts, their abundance profiles, and the formation of chimeric transcripts using RNA-seq data and genome assemblies. The transcript analysis of TEs across various species revealed significant differences in TE abundance and expression patterns. In particular, <em>Schistocerca americana</em> exhibited twice the number of transcripts within the genus Schistocerca compared to the average of other species, while <em>Gryllus bimaculatus</em> displayed the lowest number of transcripts. Despite this, all <em>Schistocerca</em> species shared similar fractions of TE transcripts at the clade level, with DNA transposons (45%) being the most abundant, followed by LINE (19%) and LTR elements (18%). Interestingly, <em>Acrida cinerea</em> displayed different TE abundance patterns compared to <em>Schistocerca</em> species, particularly with an increased proportion of LTR transcripts, accounting for 31% of the total transcripts. Further analysis revealed tissue-specific transcriptional activity of TE clades, with notable differences between male and female specimens. In <em>Gryllus bimaculatus</em>, TEs were highly transcribed across ovaries and gut tissues in females compared to male testes and gut. Conversely, <em>Gastrimargus marmoratus</em> displayed higher TE transcription in male tissues compared to females, indicating species-specific expression patterns. A similar pattern has been observed in <em>Acrida cinerea</em>, except in female gonads, where 4618 TEs were transcribed compared to 3757 in male gonads. Despite these variations, no correlation was found between genome size and TE transcript abundance. Additionally, highly conserved TEs were involved in the formation of chimeric transcripts, indicating potential regulatory roles in gene expression. The expression quantification analysis of chimeric TEs and genes revealed tissue-specific expression patterns, and TEs do not control the overall expression of all genes except some, suggesting regulatory roles of TEs in gene expression. Overall, our study underscores tissue-specific variations in TE expression and transcript abundance among different species. Additionally, our findings suggest the involvement of highly conserved TEs in the formation of chimeric transcripts across different species.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149090"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of biomarkers related to mitochondria during ex vivo lung perfusion for lung transplants based on machine learning algorithm","authors":"Zhi-Chang Yang ,&nbsp;Wen-Yuan Lu ,&nbsp;Zhen-Yang Geng ,&nbsp;Yang Zhao ,&nbsp;Xiao-Ming Chen ,&nbsp;Tong Zheng ,&nbsp;Ji-Ze Wu ,&nbsp;Kai-Jun Huang ,&nbsp;Hao-Xiang Yuan ,&nbsp;Yang Yang","doi":"10.1016/j.gene.2024.149097","DOIUrl":"10.1016/j.gene.2024.149097","url":null,"abstract":"<div><h3>Background</h3><div>Ex vivo lung perfusion (EVLP) is a critical strategy to rehabilitate marginal donor lungs, thereby increasing lung transplantation (LTx) rates. Ischemia–reperfusion (I/R) injury inevitably occurs during LTx. Exploring the common mechanisms between EVLP and I/R may unveil new treatment targets to enhance LTx outcomes.</div></div><div><h3>Methods</h3><div>We obtained datasets from the public Gene Expression Omnibus (GEO) for EVLP (GSE127055 and GSE127057) and I/R (GSE145989) processes. We performed analysis of differentially expressed genes (DEGs) and Gene Set Enrichment Analysis (GSEA). Mitochondrial genes were sourced from the MitoCarta 3.0 database. Hub mitochondrial-related DEGs (MitoDEGs) were identified using a combination of protein–protein interaction networks and machine learning methods, which were further validated in cell and mice models of EVLP.</div></div><div><h3>Results</h3><div>GSEA analysis of DEGs following EVLP and I/R revealed significant inhibition of mitochondrial function pathways, encompassing mitochondrial central dogma, mtRNA metabolism, OXPHOS assembly factors, metals and cofactors, and heme synthesis and processing processes. Machine learning algorithms including Random Forest, LASSO, and XGBoost identified five downregulated genes (MTERF1, ACACA, COX15, OSGEPL1, and COQ9) as hub MitoDEGs for both EVLP and I/R processes. We confirmed the reduced expression of these hub MitoDEGs in endothelial cells during EVLP and observed mitochondrial damage in endothelial cells characterized by swollen morphology and cristae disappearance.</div></div><div><h3>Conclusions</h3><div>Imbalance in mitochondrial homeostasis is a shared pathological process during EVLP and I/R-induced lung injury. The identified hub mitochondrial-related genes (MTERF1, ACACA, COX15, OSGEPL1, and COQ9) suggest promising therapeutic targets for lung injury during LTx. The downregulation of these genes indicates a significant disruption in mitochondrial function. This study provides potential mitochondrial-related therapeutic targets for I/R-induced lung injury and for donor lung repair during EVLP procedure in LTx.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149097"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of novel ACE2 mRNA transcripts: The potential role of alternative splicing in SARS-CoV-2 infection","authors":"Panagiotis G. Adamopoulos,&nbsp;Natalia Bartzoka,&nbsp;Panagiotis Tsiakanikas,&nbsp;Andreas Scorilas","doi":"10.1016/j.gene.2024.149092","DOIUrl":"10.1016/j.gene.2024.149092","url":null,"abstract":"<div><div>The human angiotensin converting enzyme 2 (<em>ACE2</em>) gene encodes a type I transmembrane protein, which is homologous to angiotensin I-converting enzyme (<em>ACE</em>) and belongs to the angiotensin-converting enzyme family of dipeptidyl carboxypeptidases. As highlighted by the COVID-19 pandemic, ACE2 is not only crucial for the renin-angiotensin-aldosterone system (RAAS), but also displays great affinity with the SARS-CoV-2 spike protein, representing the major receptor of the virus. Given the significance of ACE2 in COVID-19, especially among cancer patients, the present study aims to explore the transcriptional landscape of <em>ACE2</em> in human cancer and non-cancerous cell lines through the design and implementation of a custom targeted long-read sequencing approach. Bioinformatics analysis of the massive parallel sequencing data led to the identification of novel <em>ACE2</em> mRNA splice variants (<em>ACE2</em> sv.7–sv.12) that demonstrate previously uncharacterized exon-skipping events as well as 5′ and/or 3′ alternative splice sites. Demultiplexing of the sequencing data elucidated the differential expression profile of the identified splice variants in multiple human cell types, whereas <em>in silico</em> analysis suggests that some of the novel splice variants could produce truncated ACE2 isoforms with altered functionalities, potentially influencing their interaction with the SARS-CoV-2 spike protein. In summary, our study sheds light on the complex alternative splicing landscape of the <em>ACE2</em> gene in cancer cell lines, revealing novel splice variants that could have significant implications for SARS-CoV-2 susceptibility in cancer patients. These findings contribute to the increased understanding of ACE2′s role in COVID-19 and highlight the importance of considering alternative splicing as a key factor in viral pathogenesis. Undoubtably, further research is needed to explore the functional roles of these variants and their potential as therapeutic targets in the ongoing fight against COVID-19.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149092"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MALAT1 is important for facilitating HIV-1 latency reversal in latently infected monocytes","authors":"Ankita Rai ,&nbsp;Aradhana Singh ,&nbsp;Ritu Gaur ,&nbsp;Anjali Verma ,&nbsp;Nikita ,&nbsp;Sameer Gulati ,&nbsp;Rupali Malik ,&nbsp;Himanshu Dandu ,&nbsp;Abhishek Kumar ,&nbsp;Ravi Tandon","doi":"10.1016/j.gene.2024.149095","DOIUrl":"10.1016/j.gene.2024.149095","url":null,"abstract":"<div><div>Long non-coding RNAs (lncRNAs) are long RNA transcripts with length &gt;200 nucleotides that do not encode proteins. They play a crucial role in regulating HIV-1 infection, yet their involvement in myeloid cells remains underexplored. Myeloid cells are susceptible to HIV infection and contribute substantially to the latent HIV reservoir. Therefore, disruption of latency within these reservoirs is crucial for achieving a definite cure. In this study, we aimed to ascertain the role of MALAT1 lncRNA in reversal of HIV-1 latency. Latently HIV-infected cell line, U1 was treated with SAHA, followed by qRT-PCR assays to confirm HIV-1 reactivation, and MALAT1 expression was assessed. The in vitro experiments revealed a significant increase in MALAT1 expression following latency reactivation and HIV-1 infection, while its knockdown using siRNA resulted in suppression of HIV transcription, which implies that MALAT1 play a significant role in facilitating the reversal of HIV-1 latency by promoting HIV transcription. Clinical samples were analysed to measure MALAT1 and pro-inflammatory cytokines expression. The elevated MALAT1 expression in treatment-naïve subjects compared to those on ART and HIV-negative controls suggests its association with HIV replication. Moreover, correlation analysis revealed a positive association between MALAT1 expression and pro-inflammatory cytokines, TNF-α and IP-10. To conclude, MALAT1 lncRNA emerged as a crucial facilitator of HIV-1 latency reversal in latently infected monocytes by inducing the expression of pro-inflammatory factors. These findings highlight that MALAT1 could potentially be explored as the therapeutic intervention to reactivate latent cells in monocytes.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149095"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA sequencing facilitates the identification of genetic causes of Duchenne muscular dystrophy and proposes a stepwise DMD diagnostic procedure","authors":"Huaxia Luo ,&nbsp;Yidan Liu ,&nbsp;Cuijie Wei ,&nbsp;Hui Xiong","doi":"10.1016/j.gene.2024.149089","DOIUrl":"10.1016/j.gene.2024.149089","url":null,"abstract":"<div><div>A certain percentage of Duchenne muscular dystrophy (DMD) patients remain genetically undiagnosed after routine genetic testing. Accurate genetic diagnosis is crucial for determining eligibility for mutation-specific therapies and providing relatives with reliable genetic and reproductive counselling. In this study, we utilized RNA sequencing to achieve precise genetic diagnoses in three DMD patients. We identified a deep intronic variant, NC_000023.11:g. 32644691A&gt;C (NM_004006.3:c.1149+273T&gt;G), responsible for creating a novel exon in one patient. An abnormal splicing event was also observed in the second patient. Additionally, RNA sequencing of the pathological muscle samples revealed differentially expressed genes. Based on these findings, we proposed a comprehensive, stepwise diagnostic procedure for DMD. Our study suggests that RNA sequencing can be instrumental in diagnosing disease-causing intronic variants, and the proposed procedure aims to enhance the clarity and accuracy of genetic diagnoses in DMD.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149089"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate dehydrogenase a-like 6B is not essential for spermatogenesis and male fertility in mice","authors":"Xueying Huang ,&nbsp;Zhicheng Wu ,&nbsp;Peng Ren ,&nbsp;Yi Wu ,&nbsp;Changdong Lin ,&nbsp;Hongwen Zhu ,&nbsp;Peng Dai","doi":"10.1016/j.gene.2024.149100","DOIUrl":"10.1016/j.gene.2024.149100","url":null,"abstract":"<div><div>Lactate is recognized as a principal energy substrate for male germ cells. Lactate dehydrogenases (LDHs) catalyze the reversible conversion between pyruvate and lactate, which are required for male fertility. Among them, lactate dehydrogenase A-like 6B (<em>Ldhal6b</em>) has been identified as a testis-specific LDH gene. However, its precise roles in spermatogenesis remain to be elucidated. In this study, we used a <em>Ldhal6b</em> knockout mouse model to assess its impact on spermatogenesis. Our findings reveal that <em>Ldhal6b</em> knockout mice exhibit normal development and no significant alterations in male fertility. Further, LDHAL6B is localized to mitochondria and closely associated with germ granules. Nevertheless, its depletion does not result in significant abnormalities in mitochondria, germ granules or impact piRNA biogenesis. We also observed alterations in the abundance of proteins related to mitochondrial metabolism in sperm from <em>Ldhal6b</em> knockout mice, align with its specific localization to mitochondria. Overall, our results indicate that <em>Ldhal6b</em> is dispensable for both mouse development and spermatogenesis under normal laboratory conditions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149100"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and epigenetic factors affecting carotid intima-media thickness in monozygotic twins","authors":"Saho Mori ,&nbsp;Yuya Arakawa ,&nbsp;Mika Hasegawa ,&nbsp;Shiho Kato ,&nbsp;Hinako Hashimoto ,&nbsp;Saki Yoshioka ,&nbsp;Hiromichi Ueda ,&nbsp;Osaka Twin Research Group ,&nbsp;Mikio Watanabe","doi":"10.1016/j.gene.2024.149093","DOIUrl":"10.1016/j.gene.2024.149093","url":null,"abstract":"<div><h3>Background and aims</h3><div>The intima-media thickness (IMT) of the carotid artery, an indicator of subclinical atherosclerosis, varies in close association with various factors such as diabetes and immune response. The extent of changes in IMT varies among individuals owing to both genetic and epigenetic factors. In this study, we aimed to identify single nucleotide polymorphisms (SNPs) and DNA methylation patterns that affect carotid IMT in monozygotic (MZ) twins.</div></div><div><h3>Methods</h3><div>We measured the maximum IMT (IMT-Cmax) and the mean IMT in the common carotid artery wall using ultrasonography in 107 pairs of MZ twins recruited from the Osaka University Twin Registry. The genotyping of SNPs and the measurement of methylation levels were performed using a beads array, and the expression of each gene was determined by RNA sequencing. Linear regression analysis was performed on each of the two groups: one group consisted of twins randomly selected from each pair, and the other group consisted of co-twins.</div></div><div><h3>Results</h3><div>We identified a CpG site (cg02432467) on <em>HS3ST6</em> as a significant epigenetic factor in both IMT-Cmax and mean IMT analyses. The methylation level at another site (cg07927379) was negatively correlated with <em>LINC01006</em> expression and IMT-Cmax. Furthermore, there were significant differences in <em>AP2A2</em> expression and mean IMT among individuals with each genotype of the rs10902263 polymorphism.</div></div><div><h3>Conclusions</h3><div>We identified genetic and epigenetic factors associated with carotid IMT that may be useful for individualized assessments.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149093"},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-25 from Mesenchymal stem cells inhibits T cells migration and Alleviates Type 1 diabetes mellitus by Targeting CXCR3 models","authors":"Bin Zhou ,&nbsp;Na Zhou ,&nbsp;Jiaxi Jiang ,&nbsp;Xiaru Zhang ,&nbsp;Xinfeng Zhao ,&nbsp;Yang Duan ,&nbsp;Yi Zhang","doi":"10.1016/j.gene.2024.149098","DOIUrl":"10.1016/j.gene.2024.149098","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) have demonstrated promising therapeutic potential in the treatment of type 1 diabetes mellitus (T1DM); however, the underlying mechanism remains unclear. The primary pathological mechanism of T1DM involves activated T cells infiltrating the pancreas, leading to islet inflammation and the destruction of β-cells. However, the question of whether exosomes derived from MSCs can suppress the migration of T cells to the pancreas in the context of T1DM remains unresolved. In this study, we observed that miR-25 was highly expressed in MSCs exosomes and associated with signaling pathways related to cell migration. In vitro assay, we synthesized a miR-25 mimic and transiently transfected it into activated T cells, which revealed that miR-25 can effectively reduce the expression of CXCR3. Additionally, according to the in vivo T1DM mouse model, we found that there was a significant increase in miR-25 levels in T1DM mice treated with MSCs and the number of T cells decreased. Overall, our findings suggest that MSCs exosomes containing miR-25 can impede the infiltration of activated T cells into the pancreas in T1DM by repressing CXCR3 expression in these cells.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149098"},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitogenome diversity and evolution of Bos indicus cattle in India","authors":"T. Sarath Kumar,&nbsp;Sanjeev Singh,&nbsp;Indrajit Ganguly,&nbsp;S.P. Dixit","doi":"10.1016/j.gene.2024.149096","DOIUrl":"10.1016/j.gene.2024.149096","url":null,"abstract":"<div><div>Mitochondrial DNA has been widely utilized as a valuable tool for studying the evolutionary and demographic history both within and between different livestock speciesover the past three decades. Evaluation of the evolutionary history, population structure and genetic diversity is imperative for their productivity, ecosystem services, and breeding and conservation strategies for effective management. The present study included complete mitogenome of 78 cattle, out of which 33 samples belonged to 6 <em>Bos indicus</em> breeds of India. Mitogenome diversity of zebu cattle within population (π- nucleotide, haplotype diversity) was estimated using DnaSP v6 software and between populations (F_ST ratio, AMOVA analysis) was estimated using Arlequin 3.5.2.2. Ladakhi breed showed maximum (π = 0.00645) while Gir (π = 0.00042) and Tharparkar (π = 0.00053) showed minimum diversity. The diversity between the breeds of Indian cattle was 16.34 %. There were 13 and 14 haplotypes in each of I₁ and I₂ halogroups respectively suggesting that the divergence of <em>Bos indicus</em> haplotypes likely occurred within the Indian subcontinent. The <em>Bos indicus</em> and <em>Bos taurus</em> cattle lineages separated approximately 0.75 million years ago. The divergence pattern observed in zebu cattle highlighted the probability of a distinct ancestor and supported notion of independent divergence of <em>Bos indicus</em>.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149096"},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative transcriptomic and metabolomic analysis of FTO knockout and wild-type porcine iliac artery endothelial cells","authors":"Libao Xie ,&nbsp;Ninglin Fan ,&nbsp;Xiaoting Ding ,&nbsp;Taohua Zhang ,&nbsp;Wei Wang ,&nbsp;Pengyuan Ji ,&nbsp;Huijuan Wu","doi":"10.1016/j.gene.2024.149094","DOIUrl":"10.1016/j.gene.2024.149094","url":null,"abstract":"<div><div>The <em>fat mass and obesity associated</em> (<em>FTO</em>) gene, previously identified as a pivotal genetic locus associated with adiposity, has recently been linked to various cancers. In this study, we established an FTO knockout (KO) cell line in porcine iliac artery endothelial cells (PIECs) utilizing CRISPR/Cas9 technology to systematically investigate the gene’s function and effect through transcriptomic and metabolomic analysis. Our results revealed significant gene expression and metabolic profiles differences between the FTO KO and wild-type (WT) cells. Furthermore, enrichment analysis highlighted the involvement of differentially expressed genes in metabolic processes, cellular components, and molecular functions, as well as in complement and coagulation cascades, mineral absorption, glutathione metabolism, insulin signaling, fluid shear stress, and atherosclerosis pathways. The metabolomic profiling revealed clear distinctions between the FTO KO and WT cells, indicating profound modifications in cellular metabolism. Correlation analysis of transcriptomic and metabolomic data revealed a significant association between six metabolites and twenty genes, with melatonin showing specific correlations with the expression of several genes, indicating a complex regulatory network between gene expression and metabolic changes. This study provides a foundation for further research on the FTO gene’s role in cellular processes and molecular mechanisms underlying physiological and pathological conditions.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"936 ","pages":"Article 149094"},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}