Functional & Integrative Genomics最新文献

{"title":"3’UTR RNA editing driven by ADAR1 modulates MDM2 expression in breast cancer cells","authors":"Elanur Almeric,&nbsp;Deniz Karagozoglu,&nbsp;Mustafa Cicek,&nbsp;Didem Naz Dioken,&nbsp;Huseyin Avni Tac,&nbsp;Esra Cicek,&nbsp;Busra Aytul Kirim,&nbsp;Irmak Gurcuoglu,&nbsp;Osman Ugur Sezerman,&nbsp;Nurhan Ozlu,&nbsp;Ayse Elif Erson-Bensan","doi":"10.1007/s10142-025-01611-3","DOIUrl":"10.1007/s10142-025-01611-3","url":null,"abstract":"<div><p>Epitranscriptomic changes in the transcripts of cancer related genes could modulate protein levels. RNA editing, particularly A-to-I(G) editing catalyzed by ADAR1, has been implicated in cancer progression. RNA editing events in the 3’ untranslated region (3’UTR) can regulate mRNA stability, localization, and translation, underscoring the importance of exploring their impact in cancer. Here, we performed an in silico analysis to detect breast cancer enriched RNA editing sites using the TCGA breast cancer RNA-seq dataset. Notably, the majority of differential editing events mapped to 3’ untranslated regions (3’UTRs). We confirmed A-to-I(G) editing in the 3’UTRs of <i>MDM2</i> (Mouse Double Minute 2 homolog), <i>GINS1</i> (GINS Complex Subunit 1), and <i>F11R</i> (Junctional Adhesion Molecule A) in breast cancer cells. RNA immunoprecipitation with ADAR1 antibody confirmed the interaction between ADAR1 and <i>MDM2</i>, <i>GINS1</i>, and <i>F11R</i> 3’UTRs. ADAR1 knockdown revealed decreased editing levels, establishing ADAR1 as the editing enzyme. A reporter assay for <i>MDM2</i>, an oncogene overexpressed mostly in luminal breast cancers, demonstrated that RNA editing enhances protein expression, in agreement with reduced MDM2 protein levels in ADAR1 knockdown cells. Further exploration into the mechanisms of 3’UTR editing events revealed an interaction between ADAR1 and CSTF2, a core component of the polyadenylation machinery, as identified through biotin-based proximity labeling mass spectroscopy, and co-immunoprecipitation experiments. Furthermore, CSTF2 knockdown reduced both ADAR1 and MDM2 protein levels. Our findings highlight implications for <i>MDM2</i> regulation by ADAR1-dependent 3’UTR RNA editing and present an interplay between RNA editing on 3’UTRs and the mRNA polyadenylation machinery. These results improve our understanding of ADAR1’s role in cancer-associated 3’ UTR RNA editing and its potential as a therapeutic target.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01611-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074117","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":"Durum wheat nuclear factor Y (NF-Y) a subfamily: structure, phylogeny, and expression analysis in response to hormones and abiotic stresses","authors":"Yosra Chouaibi,&nbsp;Mohamed Taieb Bouteraa,&nbsp;Walid Ben Romdhane,&nbsp;Narjes Baazaoui,&nbsp;Mohammad Y. Alfaifi,&nbsp;Miroslava Kačániová,&nbsp;Natália Čmiková,&nbsp;Anis Ben Hsouna,&nbsp;Stefania Garzoli,&nbsp;Alina Wiszniewska,&nbsp;Rania Ben Saad","doi":"10.1007/s10142-025-01607-z","DOIUrl":"10.1007/s10142-025-01607-z","url":null,"abstract":"<div><p>Nuclear factor-Y (NF-Y) transcription factors are heterotrimeric complexes that are widely distributed in eukaryotes and play essential roles in many biological processes. Although NF-YA proteins have been characterized in numerous plants, their contribution to the response of durum wheat (<i>Triticum turgidum</i> ssp. <i>durum</i>) to environmental factors has not been reported. Thus, this study was aimed at identification and characterization of <i>Triticum turgidum TtNF-YA</i> family members through genome-wide analysis. Twelve <i>NF-YA</i> genes were discovered in <i>Triticum turgidum</i>. Discovered genes were distributed across eight chromosomes, while their encoded proteins were localized in cell nucleus. Structure and motif pattern analyses revealed that the <i>TtNF-YA</i> genes were relatively conserved. The expression of <i>TtNF-YAs</i> genes was significantly induced by several stressors and their expression profiles differed in various tissues and at various development stages. Notably, <i>TtNF-YA2 A-1</i> and <i>TtNF-YA2B-1</i> exhibited the greatest increase in response to Polyethylene glycol, while <i>TtNF-YA4 A</i> and <i>TtNF-YA4B-1</i> showed the highest increase under salt stress. Additionally, <i>TtNF-YA5B-1</i> and <i>TtNF-YA6 A-1</i> displayed pronounced upregulation when exposed to exogenous Abscisic acid, suggesting that <i>TtNF-YA</i> are involved in a series of cellular and developmental events. This finding was corroborated by the recognition of several <i>cis</i>-regulatory elements in the <i>TtNF-YAs</i> promoter region, associated with the applied treatments. Overexpression of <i>TtNF-YA2 A-1</i>, <i>TtNF-YA2B-1</i>, <i>TtNF-YA4 A</i>, <i>TtNF-YA4 A-1, TtNF-YA4B-1</i>, and <i>TtNF-YA5 A-2</i> genes in <i>Saccharomyces cerevisiae</i> showed that these genes increase cell tolerance to multiple stresses. Our results will facilitate subsequent functional analysis of <i>TtNF-YAs</i> genes, which emerge as promising targets for genetic engineering for increasing wheat tolerance to multiple stresses.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01607-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944205","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":"sc-MULTI-omics approach in nano-rare diseases: understanding the pathophysiological mechanism of Mulvihill-Smith Syndrome","authors":"Angelika Riess,&nbsp;Cristiana Roggia,&nbsp;Antje Schulze Selting,&nbsp;Vladislav Lysenkov,&nbsp;Stephan Ossowski,&nbsp;Nicolas Casadei,&nbsp;Olaf Riess,&nbsp;Yogesh Singh","doi":"10.1007/s10142-025-01608-y","DOIUrl":"10.1007/s10142-025-01608-y","url":null,"abstract":"<div><p>Mulvihill-Smith Syndrome (MSS) is a clinically complex and genetically unsolved nano-rare disorder with only 12 patients reported in the literature. Most patients (91%) have immunological impairments, succumb to infection, and might develop cancer later in life. Its pathogenesis remains elusive and therapeutic options are limited. We used single-cell MULTI-omics (sc-MULTI-omics), combining transcriptomics (gene expression, TCR, and BCR repertoire) and proteogenomic (Cellular Indexing of Transcriptomes and Epitopes by Sequencing; CITE-seq), to decipher the pathophysiology of nano-rare disease patient. We report a new patient who is a 16-year-old girl. She had an increased leukocyte counts and typical manifestations of MSS such as short stature, older appearance, multiple pigmented nevi, microcephaly, monolateral keratoconus, Marcus-Gunn syndrome, hearing loss, vitamin D deficiency, mild hypercortisolism, and diabetes mellitus with very high insulin resistance (T3DM). sc-MULTI-omics CITE-seq showed that the MSS patient had increased central memory CD4⁺ T cells as well as effector memory CD8⁺ T cells, whilst reduced naïve T cells (both CD4⁺ and CD8⁺ T cells). Furthermore, we identified genes and pathways associated with the progeria-like phenotype, inflammation, and cancer progression, which may contribute to the clinical signs of MSS. sc-MUTLI-omics CITE-seq analyses improve our understanding of complex human disease pathophysiology and provides an alternative approach in personalized medicine in nano-rare disease.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01608-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925628","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":"Twenty-five years of WWOX insight in cancer: a treasure trove of knowledge","authors":"Raneem Y. Hammouz,&nbsp;Izabela Baryła,&nbsp;Ewa Styczeń-Binkowska,&nbsp;Andrzej K. Bednarek","doi":"10.1007/s10142-025-01601-5","DOIUrl":"10.1007/s10142-025-01601-5","url":null,"abstract":"<p>More than two decades ago, MD Anderson Cancer group discovered, characterised, and identified the WW domain-containing oxidoreductase (WWOX) as a genes of interest mapping to the chromosomal region 16q23.3-24.2. This was pioneering research since <i>WWOX</i> is a critical tumour suppressor gene implicated in various cancers, involving interactions with numerous signalling pathways and molecular mechanisms. Notably, it inhibits the Wnt/β-catenin pathway, which is often activated in tumours. This inhibition helps prevent tumour formation by regulating cell proliferation and promoting apoptosis. Restoration of WWOX expression in cancer cell lines has been shown to reduce tumour growth and increased sensitivity to treatments. In addition to its role in tumour suppression, WWOX has been found to interact with proteins involved in critical signalling pathways such as TGF-β. Recent advancements allowed to reveal its interactions with key proteins and microRNAs that regulate cellular adhesion, invasion, and motility. Proteomic studies have shown that WWOX directly interacts with signalling molecules like Dishevelled and SMAD3, further underscoring its role in antagonizing metastasis. Challenges remain in translating this knowledge into clinical applications. For instance, the mechanisms underlying WWOX loss in tumours and its role across diverse cancer types require further investigation. Overall, <i>WWOX</i> serves as a vital player in maintaining cellular stability and preventing cancer progression through its multifaceted functions. Here, we include an updated molecular function of <i>WWOX</i> in cancers to possibly contribute to the potential use of WWOX expression as a biomarker regarding prognosis and response to the treatment.</p><p>Not applicable.</p>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10142-025-01601-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908809","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":"Establishment of a rapid RAA-CRISPR/Cas12a system targeting the recN gene for on-site detection of Streptococcus suis in livestock and fresh pork meat","authors":"Jian Yang,&nbsp;Wenjing Li,&nbsp;Yulian Hu,&nbsp;Yun Han,&nbsp;Changwei Lei,&nbsp;Hongning Wang","doi":"10.1007/s10142-025-01605-1","DOIUrl":"10.1007/s10142-025-01605-1","url":null,"abstract":"<div><p><i>Streptococcus suis</i> is a major bacterial pathogen in the swine industry, causing meningitis, arthritis, and other diseases in infected pigs. It also poses significant public health risks due to its zoonotic potential, particularly in individuals with skin lesions. Current detection methods, including traditional culture-based techniques and PCR assays, are time-consuming, labor-intensive, and lack sufficient accuracy. To address these limitations, this study aimed to develop a rapid and precise detection method for <i>S. suis</i>. By leveraging whole-genome sequencing (WGS) and multiple sequence alignment, the <i>recN</i> gene was identified as a highly specific molecular target. A novel isothermal detection method, integrating recombinase-aided amplification (RAA) with CRISPR/Cas12a, was subsequently established. This RAA-CRISPR/Cas12a-based system demonstrated superior sensitivity compared to conventional PCR (targeting the <i>gdh</i> gene), achieving detection within 30 min without requiring specialized equipment. This method achieves 2.44 × 10¹ copies/µL and 2.1 × 10¹ CFU sensitivity and 100% specificity within 30 min, outperforming conventional PCR in speed and reliability while eliminating dependency on specialized equipment. Designed for field applications, it offers a cost-effective (US$1/test), user-friendly solution for on-site <i>S. suis</i> detection in swine farms and fresh pork meat, enhancing outbreak control and preventive healthcare in the livestock industry.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143908631","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":"Genomic dissection of terminal heat tolerance in synthetic hexaploid derived nested introgression libraries of wheat (Triticum aestivum L.)","authors":"Amandeep Kaur,&nbsp;Guriqbal Singh Dhillon,&nbsp;Sandeep Kaur Dhaliwal,&nbsp;Balihar Kaur,&nbsp;Monika Garg,&nbsp;Parveen Chhuneja,&nbsp;Kuldeep Singh,&nbsp;Puja Srivastava,&nbsp;Achla Sharma,&nbsp;Satinder Kaur","doi":"10.1007/s10142-025-01604-2","DOIUrl":"10.1007/s10142-025-01604-2","url":null,"abstract":"<div><p>The terminal heat stress during grain filling period is major threat to wheat productivity. Heat tolerant QTLs were harnessed from synthetic hexaploid lines (SHWs) derived from heat tolerant <i>Ae. tauschii</i> accessions in present study. SHWs were crossed with two heat susceptible advanced breeding lines to develop nested introgression libraries (S-NILibs). The S-NILibs were evaluated for phenotypic traits and heat tolerance index (HTI) over three years under optimum environment (OE) with sowing at normal date in mid-November and heat stressed environment (HSE) under sown late during mid-December. The panel of 354 S-NILibs was genotyped using the 35 K Axiom® Wheat Breeder’s Array. Genome-wide association study (GWAS) identified a total of 61 marker-trait associations (MTAs) across environments (OE and HSE), associated with different traits using multiple models. Of these, two MTAs AX_94985380 for plant height (PH), spikelet number (SN) and AX_94469933 for plant height (PH), thousand grain weight (TGW) were observed for more than one trait across environments and models. Another MTA for HTI (AX-94461626) mapped on 4B chromosome was observed in all four environments and three models. This MTA originated from genes for Ubiquitin carboxyl-terminal hydrolases which is known for maintenance of the circadian clock at high temperature. A subset of MTAs was validated using KASP markers suggested strong association with traits of PH, SN, flag leaf length (FL) and number of productive tillers (pTN). The S-NILib generated, and QTLs identified in this study are potential pre-breeding resource for heat stress tolerance.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904858","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 metabolite and transcriptome profiles of cultivated and wild rice to unveil gene regulatory networks and key genes determining rice source and sink strength","authors":"Anuradha Singh,&nbsp;Jyotirmaya Mathan,&nbsp;Aditi Dwivedi,&nbsp;Ruchi Rani,&nbsp;Aashish Ranjan","doi":"10.1007/s10142-025-01606-0","DOIUrl":"10.1007/s10142-025-01606-0","url":null,"abstract":"<div><p>Targeting source and sink strength for crop yield increase requires a comprehensive genetic and metabolic understanding of desirable source and sink features. We performed comprehensive metabolite and transcriptomic comparisons of the photosynthetic flag leaves and milky-stage developing grains of two cultivated rice varieties (<i>Oryza sativa</i> L. ssp. <i>Indica</i> cv. IR64 and <i>Oryza sativa</i> L. ssp. <i>Japonica</i> cv. Nipponbare) and two wild rice accessions (<i>Oryza rufipogon</i> and <i>Oryza australiensis</i>). The selected wild rice accessions had stronger source strength as evidenced by a higher photosynthesis rate and more abundance of primary metabolites in the photosynthetic leaves than the cultivated varieties. In contrast, cultivated varieties had efficient sink as grains were bigger and accumulated more sugars, amino acids, and fatty acids than the selected wild rice. Transcriptomic analyses identified 9,309 genes for efficient source in wild rice, enriched for biological pathways related to photosynthesis, carbohydrate metabolism, and sucrose transport. 7,062 genes, enriched for starch biosynthesis and lipid metabolism, were associated with the efficient sink strength in the cultivated varieties. Gene co-expression networks showed 267 hub genes for source strength in wild rice that included important genes for photosynthetic reactions and sucrose metabolism. 196 hub genes for sink strength in cultivated rice included genes involved in sucrose, amino acid, and fatty acid metabolism. Gene co-expression modules further identified the candidate transcription regulators, such as zinc finger proteins and NAC for source strength and MYB55/80 and MADS64 for sink strength. Moreover, our analyses suggested a complex interplay of phytohormones regulating rice source and sink strength.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892687","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":"Mitochondrial genome evolution in the orchid subfamily Cypripedioideae (Orchidaceae)","authors":"Shiyu Qin,&nbsp;Hanchen Wang,&nbsp;Miaomiao Wang,&nbsp;Bingyi Shao,&nbsp;Chongbo Ma,&nbsp;Boyun Yang,&nbsp;Xiaohua Jin","doi":"10.1007/s10142-025-01596-z","DOIUrl":"10.1007/s10142-025-01596-z","url":null,"abstract":"<div><p>In this study, the mitogenomes of nine species in the subfamily Cypripedioideae were newly sequenced and assembled using both short and long reads for evolutionary analyses. Complete multi-chromosomal mitogenomes were obtained for <i>Cypripedium subtropicum</i>, <i>C. henryi, Phragmipedium humboldtii</i>, <i>Phr. kovachii,</i> and <i>Paphiopedilum micranthum</i>, and draft assemblies were obtained for four additional <i>Paphiopedilum</i> species. Thirty-nine protein-coding genes were annotated and shared in nine sampled species. <i>sdh4</i> was discovered in all species of Cypripedioideae, and <i>rpl10</i> was detected in four species of <i>Paphiopedilum</i>. These two genes might have been horizontally transferred from non-orchid plants at different times. Approximately 101 to 998 repeat sequences were identified with total lengths of 417,136 to 785,960 bp in the mitogenomes of Cypripedioideae. There were 634 and 662 RNA editing sites in <i>C. subtropicum</i> and <i>Pa. gratrixianum</i>, respectively, and C-to-U editing was dominant. The <i>nad</i> and <i>ccm</i> genes exhibited high frequencies of RNA editing. Our study revealed the complexity of orchid mitogenomes, including evidence for the horizontal transfer of <i>rpl10</i> and <i>sdh4.</i></p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888715","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":"RNA-binding protein HuR interacts with UFM1 mRNA to ameliorate chondrocyte inflammation, apoptosis and extracellular matrix degradation","authors":"LeXiang Li,&nbsp;Rong Zhou,&nbsp;ZhiPeng Yue,&nbsp;HaoBo Li,&nbsp;YaGuang Han,&nbsp;Lei Zhang,&nbsp;Jun Zhu","doi":"10.1007/s10142-025-01591-4","DOIUrl":"10.1007/s10142-025-01591-4","url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the mechanisms by which the RNA-binding protein HuR /ELAVL1 interacts with UFM1 <i>mRNA</i> to ameliorate chondrocyte inflammation, apoptosis, and extracellular matrix (ECM) degradation in osteoarthritis (OA).</p><h3>Methods</h3><p>OA cartilage tissues were collected. A lipopolysaccharide-induced chondrocyte inflammation model was constructed and transfected with relevant sequences or plasmids, chondrocyte viability was detected by MTT, and chondrocyte apoptosis was detected by flow cytometry. OA was induced in rats via anterior cruciate ligament transection (ACLT), and lentiviral vectors mediating overexpression or silencing of HuR/UFM1 were administered via intra-articular injection following surgery. The pathology of cartilage tissue in rats was observed by hematoxylin and eosin staining and safranin O/fast green staining, apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Collagen II, Aggrecan, MMP3, and MMP13 were measured by immunohistochemistry. Western blot was conducted to measure PCNA, Cleaved-caspase 3, Collagen II, Aggrecan, MMP3 and MMP13. Inflammatory factors in chondrocyte supernatant and rat serum were detected using an enzyme-linked immunosorbent assay. HuR and UFM1 detection was performed using real-time fluorescence quantitative PCR and Western blot. Bioinformatics software, RIP, RNA pull down and mRNA stability analysis were combined to study the binding relationship between HuR and UFM1.</p><h3>Results</h3><p>HuR expression was down-regulated in OA. HuR overexpression ameliorated OA chondrocyte inflammation, apoptosis, and ECM degradation, and HuR downregulation aggravated these pathologies. HuR regulated UFM1 stability by binding to UFM1 3’UTR. UFM1 expression was downregulated in OA and positively correlated with HuR expression. UFM1 silencing counteracted the ameliorative effect of HuR on OA chondrocyte inflammation, apoptosis, and ECM degradation.</p><h3>Conclusion</h3><p>HuR ameliorates OA chondrocyte inflammation, apoptosis, and ECM degradation through post-transcriptional regulation of UFM1.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879556","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":"SNP’s use as a potential chemotoxicity stratification tool in breast cancer: from bench to clinic","authors":"Hebatallah Ahmed Mohamed Moustafa,&nbsp;Walaa A. El-Dakroury,&nbsp;Alaa Ashraf,&nbsp;Ahmed I. Abulsoud,&nbsp;Shereen Saeid Elshaer,&nbsp;Nourhan M. Abdelmaksoud,&nbsp;Nehal I. Rizk,&nbsp;Sherif S. Abdel Mageed,&nbsp;Mohamed Bakr Zaki,&nbsp;Reda M. Mansour,&nbsp;Osama A. Mohammed,&nbsp;Mai A. Abd-Elmawla,&nbsp;Mustafa Ahmed Abdel-Reheim,&nbsp;Ahmed S. Doghish","doi":"10.1007/s10142-025-01602-4","DOIUrl":"10.1007/s10142-025-01602-4","url":null,"abstract":"<div><p>Breast cancer (BC) remains one of the most prevalent malignancies affecting women worldwide, necessitating ongoing research to improve treatment outcomes and minimize adverse effects associated with chemotherapy. This article explores the role of genetic variations, particularly single nucleotide polymorphisms (SNPs), in influencing the efficacy and toxicity of chemotherapeutic agents used in BC treatment. It highlights the impact of polymorphisms in drug metabolism and transport genes, such as UDP-glucuronosyltransferase 1A1 (UGT1A1), carbonyl reductase 1 (CBR1), and ATP-binding cassette multidrug transporter (ABCB1) on the risk of adverse effects, including cardiotoxicity and hematological toxicities. By identifying specific SNPs associated with drug response and toxicity, this research underscores the potential for personalized medicine approaches to optimize treatment regimens, enhance therapeutic efficacy, and minimize side effects in BC patients. The findings advocate for the integration of genetic screening in clinical practice to improve patient outcomes and tailor chemotherapy based on individual genetic profiles.</p></div>","PeriodicalId":574,"journal":{"name":"Functional & Integrative Genomics","volume":"25 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856482","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}