Molecular Genetics and Genomics最新文献

{"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}

{"title":"UCMSC-derived exosomal circDLGAP4 enhances HFF-1 cell proliferation and migration by promoting ZNF217 promoter H3K27 acetylation.","authors":"Yun-Lei Ma, Jia Fu, Yao-Xue Zhang, Han-Yue Xue, Yue-Yue Luo, Wei-Zhe Zhang, Shao-Jia Kuang, Jia-Qin Xu, Zun-Hong Liang","doi":"10.1007/s00438-026-02451-x","DOIUrl":"10.1007/s00438-026-02451-x","url":null,"abstract":"<p><p>Umbilical cord mesenchymal stem cells (UCMSCs) have been shown to actively participate in diabetic foot ulcer (DFU) wound healing. The human foreskin fibroblast-1 (HFF-1) cell line is a crucial and widely used in vitro model for fundamental research on DFUs. In this study, the role of UCMSC-derived exosomal circDLGAP4 in high-glucose (HG)-stressed HFF-1 cells was clarified, in particular whether it regulates the TATA-box binding protein-associated factor 15 (TAF15)/p300/zinc finger protein 217 (ZNF217) axis to enhance cell proliferation and migration. We confirmed that UCMSC-derived exosomes that contained circDLGAP4 in abundance enhanced the proliferation and migration of HG-stressed HFF-1 cells. Under an HG environment, ZNF217 was downregulated in the HFF-1 cells, whereas its overexpression promoted the proliferation and migration of the cells, an effect facilitated by its own activation via the p300-mediated H3K27 acetylation of its gene promoter. The p300 mRNA was stabilized through interaction with TAF15, while the expression of TAF15 was upregulated through its interaction with circDLGAP4. Additionally, exosomal circDLGAP4 promoted wound healing in mice with DFUs. In conclusion, UCMSC-derived exosomal circDLGAP4 enhanced HFF-1 cell proliferation and migration under HG conditions in vitro and promoted diabetic wound healing in vivo by activating the TAF15/p300/ZNF217 axis.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148032675","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":"Berberine impedes the DNA damage repair to inhibit colorectal cancer by regulating the SOX17/TCF4/PIM3 axis.","authors":"Fan Hu, Wei Wang, Mei Li, Qian Shi, Junjie Que, Pan Huang","doi":"10.1007/s00438-026-02439-7","DOIUrl":"10.1007/s00438-026-02439-7","url":null,"abstract":"<p><p>High levels of DNA damage repair (DDR) can promote the survival, immune evasion, and drug resistance of colorectal cancer (CRC) cells, consequently facilitating the advancement of CRC. This study was designed to investigate the inhibitory effect of berberine (BBR) on CRC progression and the underlying mechanism involving DDR regulation, to provide a novel theoretical basis for clinical CRC treatment. First, we found that BBR demonstrated a dose-dependent inhibition of the viability of CRC cells. BBR promoted apoptosis and suppressed the DDR in CRC cells by upregulating SOX17. Overexpression of SOX17 restrained CRC cell viability and facilitated cell apoptosis. BBR inhibited the DDR of CRC cells by inactivating the β-catenin/TCF4 pathway through the regulation of SOX17. Furthermore, TCF4 transcriptionally activated PIM3 expression. Knockdown of SOX17 partially eliminated the suppressive effects of BBR on CRC cell viability and DDR. Conversely, PIM3 silencing reversed the effects of SOX17 knockdown. In conclusion, we demonstrated BBR inhibits DDR in CRC cells via mediating the SOX17/TCF4/PIM3 axis, thereby blocking CRC progression. This regulatory axis serves as a potential therapeutic target for CRC, and BBR holds promising application prospects as a DDR inhibitor in CRC clinical intervention.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033103","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":"Genome-wide identification, in-silico characterization, and expression analysis of polygalacturonases in different fungal species.","authors":"Laiba Amin, Imran Zafar, Adil Jamal, Syed M Safeer Mehdi Bokhari, Fayez Saeed Bahwerth, Muhammad Noman","doi":"10.1007/s00438-026-02455-7","DOIUrl":"10.1007/s00438-026-02455-7","url":null,"abstract":"<p><p>Polygalacturonases (PGs) are key enzymes that hydrolyze pectin, a complex polysaccharide in plant cell walls, with essential roles in biological processes and industrial applications. This study presents a comprehensive genome-wide identification and in-silico characterization of PGs from four fungal species: Aspergillus oryzae, Aspergillus flavus, Neurospora crassa, and Rhizoctonia solani. A total of 44 PG protein sequences were retrieved from the NCBI database, confirming the presence of the Glyco_hydro_28 (GH28) domain, which is essential for pectin hydrolysis. Phylogenetic analysis using the Neighbor-Joining method revealed four major clades (A, B, C, D), with A. flavus and A. oryzae sharing a close evolutionary relationship (bootstrap support = 93%). Gene structure analysis revealed that A. flavus (Af1) and A. oryzae (Ao1) each have one exon, while Neurospora crassa (NSc1) contains one intron. Ten conserved motifs were identified, with Motif 1 present in Rz1, Rz2, and Rz5, and Motif 2 in all sequences except Ao15 and Ao16. Chromosomal mapping indicated species-specific gene distributions, with A. oryzae showing genes spread across five chromosomes. Gene expression analysis of A. oryzae under various growth conditions revealed 20 differentially expressed genes (DEGs), including 10 upregulated (e.g., Gene_Ao1, LFC = 2.50, FDR = 0.00450) and 10 downregulated (e.g., Gene_AO9, LFC = -2.87, FDR = 1.1e-05). Pathway enrichment analysis highlighted significant involvement of PGs in apoptosis (FDR = 1.2e0^-03), cell cycle regulation (FDR = 9.7e^-03), and DNA repair (FDR = 2.3e^-02). Protein-protein interaction (PPI) network analysis revealed 41 nodes and 400 edges, with an average node degree of 19.5. Structural modeling of the expressed protein LOCUS (XP_Ao1820953) with PDB ID: 5ZU2 showed high stability and flexibility, supported by molecular dynamics simulations. These results provide new insights into the evolutionary, structural, and functional roles of fungal PGs, with implications for their applications in biofuel production, food processing, and fiber retting.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033156","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":"Targeting KIF18B overcomes oxaliplatin resistance in esophageal squamous cell carcinoma via suppression of the ATR/CHK1 axis.","authors":"Wei Liu, Qianru Wang, Xiao Tan, Chunyu Cao, Bole Tian","doi":"10.1007/s00438-026-02440-0","DOIUrl":"10.1007/s00438-026-02440-0","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, frequently driven by chemotherapy resistance. Kinesin family member 18B (KIF18B) is implicated in tumor progression, but its role in ESCC chemoresistance remains unclear. To investigate KIF18B's clinical relevance and mechanistic contribution to oxaliplatin resistance in ESCC, KIF18B expression was analyzed in TCGA data, ESCC cell lines/tissues (qPCR, Western blot, IHC), and correlated with survival (Kaplan-Meier). Results showed that, KIF18B was significantly elevated in ESCC and correlated with shorter overall/progression-free survival. Knockdown reversed oxaliplatin resistance, reducing IC50 from 8.5 µM to 3 µM, restoring apoptosis, and inducing G2/M arrest. Silencing suppressed the ATR/CHK1 pathway (reduced p-ATR, p-CHK1, WEE1, CDC25A) and increased γH2AX foci. Co-IP confirmed KIF18B-ATR interaction, suggesting stabilization of DNA damage signaling. In vivo, KIF18B knockdown synergized with oxaliplatin, achieving > 80% tumor suppression and reduced Ki-67/p-ATR/p-CHK1 levels. In conclusion, KIF18B is a prognostic biomarker and therapeutic target in ESCC. Its inhibition overcomes oxaliplatin resistance by disrupting KIF18B-ATR interaction and ATR/CHK1-mediated DNA repair. Combining KIF18B targeting with chemotherapy or ATR inhibitors represents a promising strategy for refractory ESCC.</p>","PeriodicalId":18816,"journal":{"name":"Molecular Genetics and Genomics","volume":"301 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148033127","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}