Molecular Genetics and Genomics最新文献

{"title":"Genomic and molecular dynamics analysis of mefA-encoded macrolide efflux protein from Tn2009 and Tn2010 in Streptococcus pneumoniae.","authors":"Yustinus Maladan, Endah Retnaningrum, Budi Setiadi Daryono, Ratna Fathma Sari, Dodi Safari","doi":"10.1007/s00438-026-02457-5","DOIUrl":"10.1007/s00438-026-02457-5","url":null,"abstract":"<p><p>Antibiotic resistance in Streptococcus pneumoniae remains a major clinical challenge, particularly for macrolides such as erythromycin. This resistance is commonly associated with transposons Tn2009 and Tn2010 carrying the mefA gene, which encodes a macrolide efflux protein. This study investigated the genetic characteristics of mefA from Indonesian clinical isolates and elucidated its efflux mechanism using integrated genomic analysis and molecular dynamics simulations. Whole-genome sequencing confirmed the presence of Tn2009 and Tn2010 in clinical isolates. Multiple sequence alignment showed high conservation of mefA (98-100% identity), indicating strong evolutionary stability within the species. A homology model of the mefA encoded efflux protein was constructed and used for molecular docking, revealing stable erythromycin binding within the efflux channel with multiple favorable binding poses. Molecular dynamics simulations (200 ns) demonstrated structural stability of the protein, with an average root mean square deviation of 0.174 nm. Root mean square fluctuation analysis identified localized flexibility in residues Asn195-Ser199, suggesting a functionally relevant intracellular loop involved in conformational dynamics. Despite stable interactions, erythromycin remained confined within a localized channel region and did not undergo spontaneous translocation under equilibrium conditions. Steered molecular dynamics simulations indicated that ligand transport requires external force to overcome an initial energetic barrier of 553.07 kJ/mol/nm, followed by stepwise displacement through multiple transient binding sites, consistent with a multi-site relay mechanism. Umbrella sampling further revealed a rugged free energy landscape, with a maximum potential of mean force (PMF) of ~ 45 kcal/mol near the channel exit region. The PMF profile, reconstructed using WHAM across ~ 30 windows, showed well-converged overlap and multiple intermediate minima, indicating a stable sampling of the reaction coordinate. Collectively, these findings provide structural and energetic insights into mefA mediated erythromycin resistance in S. pneumoniae. The results support a mechanism involving stable substrate binding, localized conformational flexibility, and substantial energy barriers requiring active transport, highlighting potential targets for efflux inhibition strategies.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258952","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":"Unravelling genetic diversity in grain amaranth (Amaranthus hypochondriacus L.) core accessions using genome-wide SNP markers.","authors":"Jutika Boro, Hemant Kumar Yadav","doi":"10.1007/s00438-026-02464-6","DOIUrl":"10.1007/s00438-026-02464-6","url":null,"abstract":"<p><p>Grain amaranth (Amaranthus hypochondriacus L.) is a gluten-free pseudocereal with high nutritional value and notable climate resilience; however, its genome-wide population structure and genetic diversity remain poorly characterized. Given the considerable diversity observed in its gene pool, comprehensive genome-scale characterization are required to understand the genetics of important traits for effective breeding and improvement. Here, we employed Whole-Genome Sequencing (WGS) approach to generate genome-wide SNPs in a core accessions of A. hypochondriacus, leveraging the available reference genome. A total of 248 accessions, comprising Indian and some exotic accessions, were sequenced through Illumina paired-end sequencing, yielding 285,236 high-quality SNPs, with an average of ~ 20 × genome coverage. Population structure analysis identified six sub-populations among the core accessions, consistent with kinship and phylogenetic analyses, reflecting substantial genetic diversity within the genetic material used. Linkage disequilibrium (LD) analysis indicated moderate genome-wide LD, with an average decay distance of 29.8 kb, although strong LD (r² ≥ 0.8) was observed in some marker pairs. Functional annotation of 17,350 SNP-associated genes revealed enrichment of loci related to metabolic processes, stress responses, and developmental pathways, providing biological context observed genomic variation. Further, several genetically diverse accessions identified in this study offer valuable resources for future breeding efforts. Together, these results establish a robust genomic framework for A. hypochondriacus that supports future genome-wide association studies and genetic improvement efforts in grain amaranth.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258901","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":"miR-133b induces antitumor immunity in cervical cancer through modulating CMTM6/PD-L1 axis.","authors":"Wei-Ming Tan, Jia-Qi Wang, Li Li, Xu-Ji Liu, Hong-Bing Wang, Hui Zeng","doi":"10.1007/s00438-026-02426-y","DOIUrl":"10.1007/s00438-026-02426-y","url":null,"abstract":"<p><p>Immune evasion mediated by the PD-L1 pathway remains a major hurdle in the effective treatment of cervical cancer (CC). While microRNAs (miRNAs) are known to critically regulate host immune responses, their specific roles in modulating the immunosuppressive microenvironment in CC remain largely elusive. Therefore, this study aims to elucidate the scope, clinical relevance, and mechanistic actions of the novel miR-133b/CMTM6/PD-L1 axis in cervical cancer immune evasion. Through a comprehensive series of in vitro and in vivo assays, we evaluated the expression and function of miR-133b, CMTM6, and PD-L1 in CC tissues and cell lines. Our results revealed that miR-133b is significantly downregulated in CC, which strongly correlates with poor patient prognosis. Mechanistically, miR-133b directly targets CMTM6, thereby suppressing PD-L1 expression. In clinical CC tissues, miR-133b levels were negatively correlated with both CMTM6 and PD-L1. Utilizing an immune-competent murine syngeneic model, we demonstrated that miR-133b overexpression profoundly inhibited tumor growth. This tumor suppression was accompanied by enhanced intra-tumoral infiltration of CD4⁺ and CD8⁺T cells and an attenuated presence of myeloid-derived suppressor cells (MDSCs). Furthermore, co-culture experiments revealed that miR-133b-overexpressing CC cells significantly increased IFN-γ release, decreased IL-10 secretion, and attenuated T cell apoptosis effects that were mechanistically dependent on the inhibition of the CMTM6/PD-L1 axis. In conclusion, our findings establish miR-133b as a critical tumor suppressor and immune modulator in cervical cancer. By deciphering the miR-133b/CMTM6/PD-L1 regulatory network, this work provides a novel mechanistic perspective on CC immune evasion, suggesting that targeting this axis holds significant promise as a therapeutic strategy to reverse the immunosuppressive microenvironment and enhance anti-tumor immunity.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258933","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 functional characterization of a novel pathogenic DVL1 gene variant in Robinow syndrome.","authors":"Anil Kumar, Seema Rai, Ajay Kumar, Chandraniv Dey, Sudip Chakraborty, Anjana Munshi","doi":"10.1007/s00438-026-02466-4","DOIUrl":"10.1007/s00438-026-02466-4","url":null,"abstract":"<p><p>Robinow syndrome is a rare genetic disorder characterized by distinct craniofacial dysmorphism, mesomelic limb shortening and genital hypoplasia. The disorder has been reported to be inherited in an autosomal dominant as well as recessive patterns with a prevalence of 1:500000. In this study, we aimed to identify the genetic basis and structural consequences of disease in a clinically diagnosed case. A 3-months old male child from the Southwest Punjab region of India, born out of a consanguineous marriage, was presented with features including hypertelorism, midface hypoplasia, short stature, brachydactyly and genital anomalies. Whole-exome sequencing revealed a novel heterozygous pathogenic frameshift mutation, c.1644del (p.F549Sfs*125) in exon 14 of the DVL1 gene. This variant was absent in significant population databases and was therefore classified as pathogenic based on ACMG criteria. Familial segregation analysis by Sanger sequencing indicated it to be a de novo mutation since it was not observed in the parents as well as the elder male sibling. Further, comparative molecular dynamics analyses reveal that the mutation profoundly destabilizes DVL1, as the wild-type protein maintains stable Root Mean Square Deviation (RMSD), moderate flexibility, compact folding, and controlled essential motions, consistent with a properly folded, functional state. In contrast, the mutant displays persistent structural instability, excessive flexibility, loss of compactness, disrupted hydrogen-bond networks, and exaggerated collective motions, collectively indicating loss of stable dynamic features required for normal DVL1 function and likely non-functionality. In conclusion, this study reports a novel pathogenic variant in DVL1 associated with Robinow syndrome in this geographical region and highlights the importance of integrating genomic and structural analyses to understand disease mechanisms. These findings expand the mutational spectrum and have important implications for precise diagnosis, genetic counselling, and future studies on targeted molecular mechanisms.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258873","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":"Unveiling the role of heat shock protein 83 (HSP83) in Gossypium hirsutum in enhancing whitefly stress tolerance.","authors":"Muhammad Waseem Sajjad, Rubab Zahra Naqvi, Ifrah Imran, Mohammad Abubakar Yasin, Mariam Akhtar, Imran Amin","doi":"10.1007/s00438-026-02463-7","DOIUrl":"10.1007/s00438-026-02463-7","url":null,"abstract":"<p><p>Heat shock proteins (HSPs) are key molecular chaperones that control protein homeostasis and stress signalling in plants. They have been widely studied for abiotic stresses, such as drought and heat; however, their role in insect-mediated biotic stress is little known, especially in polyploid crops like cotton, which is an important economic crop. Whitefly, Bemisia tabaci (Gennadius), infestation is a serious agronomic constraint in cotton (Gossypium spp.); however, efforts to completely investigate the genetic and molecular components driving host resistance against this pest have not been entirely successful yet. In this study, a genome-wide analysis of heat shock proteins (HSPs) families in cotton varieties has been conducted to investigate the involvement of HSPs in whitefly stress. About 505 HSPs genes are found unequally distributed in the genomes of four cotton species. Chromosomal locations and their mapping have shown the highest number of genes at chromosome 9 in G. hirsutum and G. barbadense; at chromosome 6 in G. raimondii; and at chromosome 5 in G. arboreum. Gene ontology, evolutionary dynamics and domain analysis have been performed for HSP families in cotton, which showed the presence of different conserved domains important for biological as well as molecular functions. The HSP83, belonging to the HSP90 gene family, has been focused on in cotton species for this particular aspect due to the differential expression suggested by reference RNA-sequencing data. The gene structure of these HSP83s is similar, and all contain a conserved HSP90 superfamily coding for important domains like HSP90-like ATPase. In addition, various important cis-regulatory elements like bZIP, WRKY, and GT1-motif, related to different signalling and stress patterns during the central dogma, have been found in the promoter regions of HSP83s. The functional validation was done by virus-induced gene silencing (VIGS) of the target HSP83 gene found at chromosome 12 in G. hirsutum which showed increased whitefly infestation in the infiltrated plants. These results demonstrate that HSP83 is a conserved molecular regulator of cotton's resistance to whiteflies and that it aids in maintaining stress-responsive signalling networks when insects attack. HSP83's evolutionary conservation, promoter architecture, and functional validation all point to it being an important component of polyploid cotton's defensive mechanism. These results provide a molecular foundation for integrating chaperone-mediated stress regulation into crop development initiatives and further our knowledge of HSP90-family proteins in plant-insect interactions.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258942","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":"WTAP-mediated m⁶A methylation of CEP55 promotes immune evasion in lung adenocarcinoma by activating the PI3K/AKT/mTOR pathway.","authors":"Tianyu Yang, Tao Chen, Ran Yang","doi":"10.1007/s00438-026-02461-9","DOIUrl":"10.1007/s00438-026-02461-9","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is the most lethal subtype of lung cancer, and its occurrence and progression are closely correlated with immune escape. CEP55 is upregulated in a variety of malignancies and participates in tumor progression, yet its specific role in the immune regulation of LUAD remains poorly defined. Due to the unclear mechanism of immune escape, the therapeutic efficacy of immunotherapy for LUAD is still unsatisfactory. Therefore, it is essential to further elucidate the underlying molecular mechanisms and identify novel therapeutic targets. This study aims to explore the biological function of CEP55 in LUAD immune escape, as well as to clarify its upstream regulatory mechanism and downstream signaling pathways. CEP55 expression in LUAD tissues was assessed utilizing data from TCGA-LUAD and validated in cells. Bioinformatics approaches were employed to explore CEP55-enriched signaling pathways and their link to CD8⁺ T cell infiltration. A CD8⁺ T-tumor cell co-cultured model was established, and LDH release, ELISA, and CFSE staining were utilized to assess CD8⁺ T cell cytotoxicity and proliferation. To uncover the role of CEP55 in LUAD cell behavior, we employed CCK-8, EdU labeling, Transwell assays, and flow cytometry to systematically evaluate its effects on proliferation, migration, invasion, and apoptosis. Western blotting was performed to measure key signaling pathway proteins expression level. Potential upstream regulators of CEP55 m⁶A modification were identified through database mining, followed by validation using RIP, MeRIP-qPCR, and WB. CEP55 was highly expressed in LUAD and inversely associated with CD8⁺ T cell infiltration. Knockdown of CEP55 in LUAD enhanced tumor-killing activity of CD8⁺ T cells in a co-culture system and significantly suppressed LUAD cell proliferation, migration, invasion, and anti-apoptotic capacity. CEP55 was positively correlated with WTAP in LUAD. WTAP stabilized CEP55 mRNA expression via m⁶A modification, while CEP55 activated the PI3K/AKT/mTOR pathway, upregulating PD-L1. This led to CD8⁺ T cell exhaustion and promoted tumor immune evasion. This study reveals a critical mechanism whereby WTAP upregulates CEP55 expression via m⁶A modification, thereby activating the PI3K/AKT/mTOR signaling pathway, inhibiting the anti-tumor activity of CD8⁺ T cells, and ultimately facilitating LUAD progression. These findings indicate that CEP55 serves as a promising therapeutic target for LUAD immunotherapy, providing novel theoretical evidence to improve the efficacy of immune treatment.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258950","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":"Integrated multi-technology exploration of the mechanism by which Badushengji San regulates core targets in diabetic foot ulcer.","authors":"Yifan Cai, Aizhen Lin, Junyi Shen, Xiaoyu Zhang, Jinbo Zhou, Yuanzhi Rang, Xiaoyin Chen","doi":"10.1007/s00438-026-02469-1","DOIUrl":"10.1007/s00438-026-02469-1","url":null,"abstract":"<p><p>Diabetic Foot Ulcer (DFU), a prevalent and refractory diabetic complication, lacks clear pathological targets and effective therapeutic strategies. This study aimed to identify potential DFU biomarkers and preliminarily explore the mechanism of Badushengji San (BDS) in treating DFU. Transcriptome datasets (GSE199939, GSE134431) and single-cell RNA sequencing (scRNA-seq) data (GSE165816) were retrieved to screen differentially expressed genes (DEGs) and DFU-related cell subsets. Intersection genes among DEGs, drug targets, and high-dimensional Weighted Gene Co-Expression Network Analysis (hdWGCNA) genes were then identified. Core biomarkers were subsequently screened using Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Boruta algorithms. Macrophages were defined as DFU-associated core cells. Three biomarkers (CYCS, HMOX1, UPP1) showed diagnostic value (the area under the curve (AUC) of UPP1 = 0.973). BDS (50 ng/mL) reversed 40 mM glucose-induced L929 cell injury by restoring HMOX1 and suppressing UPP1 expression. These biomarkers were enriched in pathways like nuclear factor-kappa B (NF-κB), and their abnormal expression was closely linked to DFU pathological progression. Notably, Benzoyl paeoniflorin had the lowest binding energy (-10.06 kcal/mol) with UPP1. Collectively, this study identified CYCS, HMOX1, and UPP1 as potential biomarkers for DFU and preliminarily revealed the potential regulatory effect and molecular characteristics of BDS in DFU intervention, which lays a bioinformatic foundation and provides preliminary experimental clues for further in vivo mechanism research.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258923","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":"Therapeutic target exploration of Shugan Jianpi formula in liver fibrosis: an integrated lncRNA-mRNA co-expression network analysis.","authors":"Kaiqiang Wan, Qiong Zhou, Ruirui Feng, Chang Fan, Weibing Shi, Wenbin Xu, Hui Jiang, Qiumei Zhou","doi":"10.1007/s00438-026-02437-9","DOIUrl":"10.1007/s00438-026-02437-9","url":null,"abstract":"<p><p>Shugan Jianpi Formula (SGJPF), a traditional Chinese herbal formulation, has been clinically used for decades in the management of various chronic liver diseases, including liver fibrosis (LF). Previous studies have demonstrated the efficacy of SGJPF in ameliorating pathological manifestations in murine models of LF. However, the precise molecular mechanisms underlying its therapeutic effects remains unclear. In the present study, we aimed to explore the therapeutic mechanisms of SGJPF through comprehensive analysis of LncRNA-mRNA co-expression network.The therapeutic efficacy of SGJPF in a CCL₄-induced LF murine model was assessed by histopathological alterations, α-smooth muscle actin (α-SMA) and collagen Ⅰ expression. To elucidate the molecular mechanisms underlying the efficacy of SGJPF, whole transcriptome RNA sequencing technology was conducted to identify the LncRNAs and mRNAs expression profiles across control, model, and SGJPF-treated groups. GO function and KEGG pathway enrichment analysis was performed to identify the biological functions and signaling pathways associated with the differentially expressed genes (DEGs). Subsequently, the hub LncRNAs and mRNAs were identified based on fold change and correlation analysis. Finally, biological relevance of these core genes were further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in mouse liver tissue, revealing the regulatory interactions between LncRNAs and their target mRNAs. Compared with the control group, 401 differentially expressed (DE) LncRNAs and 1224 DE mRNAs were found in the model group. In addition, compared with the model group, 98 DE LncRNAs and 147 DE mRNAs were identified following treatment with SGJPF. Subsequently, 31 DE LncRNAs and 39 DE mRNAs were obtained and served as potential target genes of SGJPF. Functional annotation of the 31 DE LncRNAs revealed predominant involvement in small molecule metabolic processes, with significant associations observed in circadian rhythm regulation, p53 signaling pathway, TGF beta signaling pathway, and Hippo signaling pathway. Correlation analysis indicated significant associations between these 31 DE LncRNAs and 39 DE mRNAs (|PCC|> 0.65, P < 0.05). Additionally, the expression of 2 LncRNAs (Gm28857, D030074P21Rik) and 5 mRNAs (Cdkn1a, Id1, Id4, Wnt9b, Gadd45g) were confirmed by RT-qPCR in mouse liver tissue, which were consistent with RNA sequencing data. This study delineates the comprehensive LncRNA/mRNA expression profiles in LF treated with SGJPF, which may provide valuable insights into the molecular mechanisms underlying LF pathogenesis and identifying potential therapeutic targets for further investigation.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150418","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 genome analysis of carbapenemase-producing Pseudomonas aeruginosa: gene diversity, clonal distribution, and genome dynamics.","authors":"Narjes Noori Goodarzi, Farzad Badmasti","doi":"10.1007/s00438-026-02453-9","DOIUrl":"10.1007/s00438-026-02453-9","url":null,"abstract":"<p><p>Carbapenem-resistant Pseudomonas aeruginosa (CRPA) represents a major health threat due to its extensive resistance to last‑resort antibiotics. Although carbapenemase determinants are key drivers of global CRPA dissemination, comprehensive genomic investigations delineating their chromosomal versus plasmid contexts are sparse. Therefore, in this study we conducted an integrated comparative genomic analysis of P. aeruginosa strains harboring major carbapenemase genes (bla_GES, bla_KPC, bla_SPM, bla_NDM, bla_VIM, and bla_IMP), with a focus on their genomic localization, surrounding genetic architectures, and associated mobility elements. Chromosomes and plasmids carrying carbapenemase genes (retrieved from GenBank through 2025) were systematically characterized for sequence types, genetic environments, co‑occurring antimicrobial resistance genes (ARGs), and plasmid mobility features using established bioinformatic pipelines. Genetic relatedness of plasmids was inferred via ClustAGE and UPGMA clustering. Multilocus sequence typing (MLST) was employed to assess clonal relatedness of isolates. Among 398 carbapenemase-carrying genomic fragments, bla_VIM, bla_KPC, and bla_GES were the most prevalent. bla_VIM, bla_IMP, and bla_NDM showed broad geographic distribution. High-risk clones including ST235, ST111, ST233, ST357, ST308, and ST277 were among the most common sequence types. Notably, a minority (10.28%) of carbapenemase-carrying plasmids were predicted to be conjugative or mobilizable. The mex, and opr families, and sul1 were most frequent co-existing ARGs. These findings highlight the dominant role of established high-risk lineages and integrative mobile elements in shaping the epidemiology of resistance. The relatively low frequency of self-transmissible plasmids suggests that horizontal resistance dissemination is likely mediated through a combination of integrative mobile genetic elements and clonal expansion. Our results underscore the necessity for enhanced genomic surveillance strategies that integrate clonal tracking with mobile resistance determinant monitoring to better understand and control the spread of carbapenem resistance.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150319","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-binding protein hnRNPD induces epithelial-mesenchymal transition in Wilms' tumor via facilitating MAP4K4 mRNA stability.","authors":"Gang Li, Man Liao, Haibin Bao, Haolun Xu, Jun Wang, Man Zhang, Can Li, Tian Zheng, Chunlei Yang","doi":"10.1007/s00438-026-02446-8","DOIUrl":"10.1007/s00438-026-02446-8","url":null,"abstract":"<p><p>Wilms' tumor (WT) is one of the most common pediatric abdominal malignancies. The RNA-binding protein heterogeneous nuclear ribonucleoprotein D (hnRNPD) is related to cancer progression through regulating target mRNA stability. Nonetheless, its expression profile and value for WT are largely unexplored. Human renal proximal tubular epithelial cells (RPTEC) and WT cells (17.94, HFWT) were employed as experimental models for exploring hnRNPD's effect on WT progression. Subsequently, potential downstream targets of hnRNPD were identified through bioinformatics analysis. Functional validation was performed in vitro by modulating hnRNPD and its candidate targets via gene silencing and overexpression methods. Alterations in gene expression was analyzed through qRT-PCR as well as Western blot. Besides, CCK-8 was conducted to evaluate cell proliferation, whereas scratch and Transwell assays to determine cell migration alongside invasion separately. Additionally, critical epithelial-mesenchymal transition (EMT)-associated protein expression, namely E-cadherin, N-cadherin, alongside vimentin, was detected to assess regulatory impact of hnRNPD on the EMT process. hnRNPD mRNA and protein expression significantly elevated within 17.94 and HFWT cells than in RPTEC cells. Silencing of hnRNPD in 17.94 cells inhibited cell proliferation, migration, and invasion. Concurrently, N-cadherin and Vimentin protein levels declined, and E-cadherin protein level increased. Conversely, overexpression of hnRNPD in HFWT cells markedly enhanced their malignant phenotypes and promoted EMT. Bioinformatics analysis identified mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) as a potential downstream target of hnRNPD in WT. Mechanistically, hnRNPD overexpression extended the half-life of MAP4K4 mRNA, and a specific physical interaction between hnRNPD protein and MAP4K4 mRNA was observed. Functional rescue experiments further demonstrated that silencing MAP4K4 inhibited tumor malignant progression, while overexpression of MAP4K4 reversed the tumor-suppressive effects induced by hnRNPD silencing. hnRNPD may promote EMT in WT cells by stabilizing MAP4K4 mRNA, suggesting a critical role for the hnRNPD-MAP4K4 axis in driving tumor progression.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148150330","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}