Genes & genomics最新文献

{"title":"Analysis of genetic mutation characteristics in 40 Chinese patients with hepatocellular carcinoma.","authors":"Shaoshao Xu, Lei Li, Dongchang Yang, Tao Liu, Binyu Liu, Qingqing Xun, Yanrong Liu","doi":"10.1007/s13258-026-01743-1","DOIUrl":"10.1007/s13258-026-01743-1","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is notable for its marked molecular heterogeneity and poor response to systemic therapy. Targeted next-generation sequencing (NGS) has facilitated the profiling of somatic alterations in HCC. However, the interpretation of panel-based genomic features such as tumor mutational burden (TMB), copy number alterations, and candidate gene fusions remains challenging, particularly in HBV-endemic Asian populations.</p><p><strong>Objective: </strong>To explore the somatic mutation landscape of HCC using a targeted sequencing panel in a regional cohort and to descriptively assess its associations with clinicopathological characteristics.</p><p><strong>Methods: </strong>We conducted a 671-gene targeted NGS panel covering approximately 2.5 Mb of coding regions on tumor-normal paired samples from 40 patients with HCC and integrated the mutational profiles with clinicopathological data. We analyzed somatic mutations, copy number variation signals, and candidate fusion events. We performed functional enrichment analyses and comparative analyses with the Cancer Genome Atlas (TCGA) cohort. Survival analyses were conducted in an exploratory manner.</p><p><strong>Results: </strong>TP53 was the most frequently mutated gene (55%) and its mutation status was associated with hepatitis B virus infection, higher Edmondson-Steiner grade, and microvascular invasion. Panel-derived TMB values were evaluated descriptively, and exploratory survival analyses suggested potential differences between patient subgroups. Two candidate in-frame fusion signals, KIT-PDGFRA and ROS1-FBXL17, were detected in individual samples based on targeted DNA sequencing. Functional enrichment analyses indicated that mutated genes were mainly associated with cancer-related biological processes.</p><p><strong>Conclusions: </strong>This study provides an exploratory overview of somatic alterations detected by a targeted sequencing panel in a regional HCC cohort. Given the limitations inherent to panel-based analyses and the lack of independent validation, these findings should be interpreted cautiously and primarily serve as a reference for future large-scale and experimentally validated studies aimed at refining precision oncology strategies in HCC.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"595-608"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142108","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":"Synergistic antitumor activity of CAR-NK cells combined with CAR-macrophages for pancreatic cancer treatment.","authors":"Dana Jung, Seo-Gyeong Jo, Eun-Yeung Gong, Ji-Hoon Kim, Kyungsoo Ha, Gabbine Wee, Seok Jae Huh, Young-Hee Jeoung, Seok-Ho Kim","doi":"10.1007/s13258-025-01733-9","DOIUrl":"10.1007/s13258-025-01733-9","url":null,"abstract":"<p><strong>Background: </strong>Adoptive cell therapies employing chimeric antigen receptors (CARs) have achieved remarkable success in hematologic malignancies, yet their efficacy in solid tumors remains limited due to the immunosuppressive tumor microenvironment (TME), which restricts immune cell infiltration and persistence. While CAR-NK cells provide potent cytotoxicity with a favorable safety profile, their tumor penetration is often suboptimal. In contrast, macrophages possess intrinsic tumor-homing and tissue-remodeling abilities that could help overcome these barriers.</p><p><strong>Objective: </strong>This study aimed to develop a combinatorial innate-cell immunotherapy integrating nanobody-based mesothelin (MSLN)-targeting CAR-macrophages (CAR-Ms) with CAR-NK cells to remodel the TME and enhance antitumor immunity in pancreatic cancer.</p><p><strong>Methods: </strong>Using a validated D3 nanobody CAR construct, CAR-Ms were generated from PMA-differentiated THP-1 monocytes and characterized for CAR expression, M1/M2 polarization, migration, phagocytosis, and cytokine secretion. CAR-NK cell migration and cytotoxicity were evaluated using conditioned media (CM) from CAR-M/tumor co-cultures. Synergistic antitumor activity was assessed in an orthotopic MSLN⁺ pancreatic ductal adenocarcinoma (PDAC) model.</p><p><strong>Results: </strong>D3-CAR-Ms exhibited robust CAR expression (> 90%) and sustained an M1-like phenotype (CD86⁺HLA-DR⁺CD204⁻) even after tumor engagement. Functionally, they displayed enhanced migration and infiltration into MSLN⁺ PANC-1 spheroids, along with increased phagocytic and tumoricidal activity. Upon antigen engagement, CAR-Ms secreted high levels of CXCL9, which promoted CAR-NK chemotaxis, degranulation, and cytotoxicity. Sequential administration of CAR-Ms and CAR-NK cells in vivo led to marked tumor regression and durable responses without systemic toxicity.</p><p><strong>Conclusion: </strong>Combinatorial nanobody-based CAR-M and CAR-NK therapy reprograms the TME and establishes a CXCL9-driven feed-forward loop between macrophages and NK cells, leading to synergistic innate immune activation and potent tumor control. This strategy provides a mechanistically grounded and translationally feasible framework for next-generation CAR-based immunotherapies targeting MSLN-expressing solid tumors.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"523-532"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105247","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":"Multiple machine learning algorithms construct cuproptosis genes and oxidative stress genes-related LncRNAs signature with prognostic and therapeutic relevance in ovarian cancer.","authors":"Ruyue Pan, Yan Yang, Qinghuo Kong, Xin Hu, Jie Yu, Jiaxu Chen","doi":"10.1007/s13258-025-01712-0","DOIUrl":"10.1007/s13258-025-01712-0","url":null,"abstract":"<p><strong>Background: </strong>Cuproptosis and oxidative stress (COS) are emerging regulators in cancer biology. However, their link to long non-coding RNAs (lncRNAs) and clinical outcomes in ovarian cancer remains unclear.</p><p><strong>Objective: </strong>This study aimed to construct and validate a prognostic signature based on COS-related lncRNAs to improve risk stratification and provide insights into therapeutic strategies for ovarian cancer.</p><p><strong>Methods: </strong>RNA-seq and clinical data from TCGA and GEO were analyzed to identify COS-related lncRNAs via WGCNA and Pearson correlation. Prognostic lncRNAs were screened using Cox regression and modeled using multiple machine learning algorithms. Immune profiles, mutation patterns, drug sensitivity, and experimental validation were performed.</p><p><strong>Results: </strong>A 12-lncRNA signature was established that stratified patients into high- and low-risk groups with significant survival differences (HR = 22.6145, p < 0.001). The model showed strong predictive performance (AUCs: 0.91/0.967/0.974) and was validated externally. High-risk patients exhibited greater mutation burden, altered immune pathways (interferon, TGF-β), and differential predicted sensitivity to agents like Axitinib and Pazopanib. RT-qPCR confirmed the expression patterns of 11 out of 12 lncRNAs.</p><p><strong>Conclusion: </strong>This study proposes a robust 12-lncRNA signature linking cuproptosis and oxidative stress with prognosis and therapy response in ovarian cancer, offering preliminary insights for personalized treatment guidance.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"583-594"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145632054","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":"Genome-wide identification and expression analysis of the Hsf gene family in Rhododendron molle under heat stress.","authors":"Jieyu Peng, Shida Xu, Fanyu Zeng, Xingmin Geng, Jinliang Zhou","doi":"10.1007/s13258-025-01731-x","DOIUrl":"10.1007/s13258-025-01731-x","url":null,"abstract":"<p><strong>Background: </strong>Rhododendron possesses significant ornamental and economic value; however, its limited heat tolerance severely hinders its broader development and application. Heat shock transcription factors (Hsfs) are extensively involved in various abiotic stress responses and play essential roles in plant thermotolerance and other physiological processes.</p><p><strong>Objective: </strong>To identify Hsf genes in the genome of Rhododendron molle (R. molle) and investigate their regulatory mechanisms underlying heat tolerance in R. molle.</p><p><strong>Methods: </strong>The Hsf gene family was systematically identified using the genomic data of R. molle, and the expression levels of RmHsf genes under heat stress were analyzed through Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR).</p><p><strong>Results: </strong>The RmHsf gene family consists of 25 members distributed across 12 chromosomes. Phylogenetic analysis demonstrated that the RmHsf genes are classified into three subfamilies: A, B and C. Most genes within the same subfamily share similar conserved motifs and gene structures. The cis-acting elements in the promoter regions of RmHsf genes are associated with plant hormone signaling and stress response pathways. Collinearity analysis revealed that the expansion of the RmHsf gene family primarily occurred through segmental and tandem duplication events. RT-qPCR results showed that RmHsfA2, RmHsfA3, RmHsfA7a, and RmHsfA7b were significantly upregulated under heat stress, suggesting that they may serve as key genes in the heat stress response of R. molle. Among them, RmHsfA2 and RmHsfA3 were notably induced by exogenous ethylene.</p><p><strong>Conclusion: </strong>This study conducted a comprehensive genome-wide analysis of the Hsf gene family in R. molle, laying a solid foundation for functional validation of Hsf genes and the breeding of heat-tolerant cultivars.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"509-522"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951761","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":"UBL4A as a suppressor of intracerebral hemorrhage by binding to MAPK14 and promoting MAPK14 ubiquitination.","authors":"Yuyang Ou, Chen Chen, Ziyi Wang, Xi Zhu, Yaoxing Luo, Shulin Li, Dan Li","doi":"10.1007/s13258-025-01723-x","DOIUrl":"10.1007/s13258-025-01723-x","url":null,"abstract":"<p><strong>Background: </strong>Intracerebral hemorrhage (ICH) is a primary non-traumatic parenchymal hemorrhage of the brain with a high mortality and disability rate. Acupuncture has been proved to alleviate neurological deficits after ICH.</p><p><strong>Objective: </strong>Our previous study found that UBL4A is up-regulated in the ICH rat treated with acupuncture, and may be a potential molecular target for acupuncture treatment of ICH. However, the molecular mechanism behind UBL4A is unclear.</p><p><strong>Methods: </strong>UBL4A knockdown was conducted in ICH rats with acupuncture treatment to explore its role in the therapeutic effects of acupuncture on ICH. In vitro, the effects of UBL4A on heme-induced neuronal injury were evaluated using E18 rat embryonic primary cortical neurons. Proteomic experiments were used to verify the regulatory relationship between UBL4A and MAPK14.</p><p><strong>Results: </strong>UBL4A knockdown has opposite effects to the therapeutic effects of acupuncture on ICH, including increasing corner turn score, brain water content and the number of degenerated and apoptotic neuron in ICH rats. UBL4A knockdown increased the level of ROS, OPA1-S/L, p-MAPK14 and mitochondrial Drp1, and decreased mitochondrial membrane potential, ATP level and MFN2 level in rat brain tissue. In vitro, UBL4A overexpression reduced ROS level and mitochondrial membrane potential and inhibited the activation of the MAPK14/Drp1 signaling pathway. Co-IP verified the binding of UBL4A and MAPK14, and MAPK14 overexpression reversed the effect of UBL4A on hemin-induced neuronal apoptosis and ROS level.</p><p><strong>Conclusion: </strong>Our study confirms that UBL4A is involved in the therapeutic effect of acupuncture on ICH, and affects mitochondrial damage and oxidative stress through MAPK14 ubiquitination.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"571-582"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029306","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":"Integrative transcriptomics defines CD36 as a key regulator of immunometabolic signaling in acute myeloid leukemia.","authors":"Muhammad Sameer Ashaq, Qian Zhou, Yanxia Li, Meiqi Guo, Shujing Zhang, Lingling Wang, Zhuoran Li, Yi Wang, Yufeng Huang, Zhida Shi, Yuan Li, Baobing Zhao","doi":"10.1007/s13258-025-01728-6","DOIUrl":"10.1007/s13258-025-01728-6","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is characterized by extensive immunometabolic rewiring that drives leukemic progression and fosters immune evasion.</p><p><strong>Objective: </strong>This study investigates regulatory role of CD36 as an immunometabolic mediator in AML pathogenesis.</p><p><strong>Methods: </strong>Integrated bulk transcriptomics, single-cell RNA sequencing, and in-vitro validation were performed. Macrophage co-localization was validated using colorectal cancer (CRC) spatial transcriptomics.</p><p><strong>Results: </strong>CD36 was identified as a central hub in preserved immunometabolic modules, enriched for TLR signaling, lipid metabolism, antigen-presenting pathways, and cytokine-cytokine receptor interactions. Drug sensitivity analysis revealed that high CD36 expression showed greater sensitivity to venetoclax and GSK626616AC. CD36 drives AML immune cycle and revealed a strong association with AML functional states, including inflammation, differentiation, apoptosis, invasion, quiescence, and hypoxia. Single-cell analysis indicated CD36 upregulation in monocyte and macrophage clusters, facilitating ligand-receptor communication with T cells, which emphasizes CD36's role in shaping immune microenvironment. Spatial transcriptomics analysis of colorectal cancer confirmed a significant CD36-CD68 colocalization in macrophages. CD36 also influenced monocyte to macrophage differentiation in AML cells. CD36 deficiency significantly reduces AML cells' proliferation and leads to G0/G1 phase expansion, accompanied by E2F4/E2F5/RB1 modulation. Hallmark enrichment analysis unveiled that CD36-high expression leukemic cells, CD36 immune signatures, and monocytes/macrophages showed enrichment in key immune and inflammatory pathways, including TNFα/NF-κB, IL6/JAK/STAT3, and IL2/STAT5 signaling, mTORC1 activation, interferon alpha and gamma responses, and reactive oxygen species pathways.</p><p><strong>Conclusion: </strong>Integration of transcriptomics and spatial validation revealed robust CD36-mediated immunometabolic signaling in AML, which further requires comprehensive in-vitro and in-vivo validation.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"487-507"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899972","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":"Epitranscriptomic regulation of NVP-BEZ235 resistance in ccRCC via the YTHDF3-SYNM regulatory pathway.","authors":"Ruiang Wang, Cheng Lu, Erchang Shen, Xi Zhang, Xinchi Xu, Xiaoyang Cao, Tian Rao, Xiaohan Ren, Yiyang Liu, Chen Xu, Xiaoxiang Wang","doi":"10.1007/s13258-026-01737-z","DOIUrl":"10.1007/s13258-026-01737-z","url":null,"abstract":"<p><strong>Background: </strong>NVP-BEZ235 is a dual PI3K/mTOR inhibitor with promising antitumor activity in clear cell renal cell carcinoma (ccRCC). However, the mechanisms underlying acquired drug resistance remain incompletely defined.</p><p><strong>Objective: </strong>To investigate whether epitranscriptomic regulation-specifically N6-methyladenosine (m6A) modification and its reader YTHDF3-drives reversible, non-genetic resistance to NVP-BEZ235 in ccRCC, and to identify key downstream effector genes.</p><p><strong>Methods: </strong>NVP-BEZ235-resistant models were established from 786-O and PTEN-deficient Caki-1ko ccRCC cells via chronic drug exposure. Drug withdrawal assays were performed to evaluate the reversibility of resistance. Expression of m6A regulators was assessed by qRT-PCR and Western blotting. YTHDF3 was silenced using lentiviral shRNA, and changes in NVP-BEZ235 sensitivity were evaluated by CCK-8 and cell-cycle assays. Genome-wide m6A-RIP-seq and RNA-seq were integrated to define transcripts with coordinated changes in m6A methylation and expression, and core causal genes for ccRCC were prioritized by summary-based Mendelian randomization (SMR). YTHDF3-RNA interactions and dynamic m6A changes were validated by RIP-qPCR and MeRIP-qPCR, and the functional role of SYNM was tested by loss-of-function studies.</p><p><strong>Results: </strong>NVP-BEZ235-resistant cells displayed a reversible, nonheritable phenotype, partially regaining drug sensitivity after short-term drug withdrawal. YTHDF3 was selectively upregulated in resistant cells, and its knockdown significantly lowered the IC50 of NVP-BEZ235 and suppressed proliferation. Integrated m6A-RIP-seq/RNA-seq analyses revealed extensive reprogramming of m6A methylation, and SMR identified SYNM as a core m6A-regulated gene associated with increased ccRCC risk. SYNM was overexpressed in ccRCC tissues and positively correlated with YTHDF3 expression. YTHDF3 bound SYNM mRNA in resistant cells, while m6A levels and expression of both YTHDF3 and SYNM were dynamically reversible upon drug withdrawal. Silencing SYNM robustly resensitized resistant cells to NVP-BEZ235.</p><p><strong>Conclusions: </strong>Reversible resistance to NVP-BEZ235 in ccRCC is driven, at least in part, by an m6A-dependent YTHDF3-SYNM axis. Targeting YTHDF3 or SYNM may provide a rational strategy to overcome PI3K/mTOR inhibitor resistance in ccRCC.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"533-548"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051686","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":"Genome wide characterization and expression profiling of protein disulfide isomerase (PDI) gene family members in watermelon under cold stress.","authors":"Nihar Sahu, Uzzal Somaddar, Ga-Eun Bok, Dhanasekar Divya, Ijaz Yaseen, Hoy-Taek Kim, Bo-Kook Jang, Jong-In Park","doi":"10.1007/s13258-026-01751-1","DOIUrl":"10.1007/s13258-026-01751-1","url":null,"abstract":"<p><p>BACKGROUND: Protein Disulfide Isomerases (PDIs) are essential molecular chaperones that guide proteins to fold correctly by forming disulfide bonds, which are essential for protein stability and helping plants cope with stress. However, PDIs in watermelon (Citrullus lanatus) have not been explored. OBJECTIVE: This study focused on identifying and analyzing the PDI gene family in watermelon, with particular attention to their functions during exposure to cold stress. METHODS: Sixteen Citrullus lanatus PDI (ClPDI) genes were identified and analyzed for their evolutionary relationships, gene structure, regulatory elements, gene duplications, conserved motifs, miRNA targets, phosphorylation sites, and predicted 3D protein models. Gene expression under cold stress was examined in tolerant (SW66) and sensitive (PPI526233) watermelon genotypes. In addition, antioxidant enzyme activities were assessed. RESULTS: All sixteen ClPDI genes were distributed across nine watermelon chromosomes and contained thioredoxin domains, forming ten evolutionary clusters. One gene duplication event was identified within watermelon, along with fifteen orthologous relationship shared with Arabidopsis and rice. Promoter analysis revealed common abiotic stress related regulatory elements. Expression analysis showed that twelve of the sixteen ClPDI genes were upregulated (≥ 2 fold) in the tolerant genotype under cold stress, with ClPDI6, ClPDI8, and ClPDI15 exhibiting ≥ 100 fold induction. Antioxidant enzyme activities were higher in the tolerant genotype than in the sensitive genotype following cold stress. CONCLUSION: The study highlights the important role of the PDI gene family in watermelon under cold stress and suggests that enhanced antioxidant activity may help maintain a favorable redox environment for proper PDI function. These findings provide potential molecular targets for improving cold stress tolerance in watermelon.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"619-632"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147354886","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":"Novel citrivirus and prunevirus genomes further demonstrate the recurrent, independent acquisition of nucleic acid-binding proteins in the family Betaflexiviridae.","authors":"Hyerin Park, Dongjin Choi, Seungwoo Baek, Myeung Seok Choi, Yoonsoo Hahn","doi":"10.1007/s13258-026-01742-2","DOIUrl":"10.1007/s13258-026-01742-2","url":null,"abstract":"<p><strong>Background: </strong>Some plant RNA viruses in the family Betaflexiviridae encode a nucleic acid-binding protein (NABP), which enhances viral infectivity. Until recently, Salvia divinorum RNA virus 1 (SdRV1) was the only known member of the genus Citrivirus to encode a NABP.</p><p><strong>Objective: </strong>This study aimed to identify novel Betaflexiviridae genomes encoding NABPs and to investigate their evolutionary origins through comparative and phylogenetic analysis.</p><p><strong>Methods: </strong>Publicly available plant transcriptome datasets were screened to identify Betaflexiviridae-like viral sequences. Twelve viral genome contigs corresponding to ten distinct viruses were assembled and annotated. Phylogenetic trees were constructed using replicase and NABP protein sequences.</p><p><strong>Results: </strong>Six putative novel species were identified within the genera Citrivirus, Prunevirus, and a potential new genus. Aquilaria sinensis virus 1 (AquSiV1) encoded a NABP, making it the second known Citrivirus with a putative copy of this gene. Hippophae rhamnoides virus 1 (HipRhV1), which also encoded a NABP, formed a distinct lineage, possibly representing a novel genus. Phylogenetic analysis of NABPs revealed topologies incongruent with the replicase phylogeny, suggesting recurrent, independent acquisition events.</p><p><strong>Conclusion: </strong>These findings expand the known genomic and taxonomic diversity of the genera Citrivirus and Prunevirus, and support the hypothesis that NABP genes have been independently and repeatedly acquired within the family Betaflexiviridae.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"609-618"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142112","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":"Anticancer agent FTY720 upregulates cell cycle regulator BTG2 via the SET/TAF-Iβ -PP2A-SMAD3 signaling pathway and induces G2/M arrest in leukemia.","authors":"Jieun Park, Yugyeong Kim, Hyebin Park, Geonhui Yun, Sang Beom Seo","doi":"10.1007/s13258-026-01739-x","DOIUrl":"10.1007/s13258-026-01739-x","url":null,"abstract":"<p><p>BACKGROUND: FTY720-mediated disruption of the SET/TAF-Iβ–PP2A complex induces distinct transcriptional changes, highlighting BTG2 as a consistently upregulated target across leukemia models. Integrated analyses reveal that FTY720 suppresses ERK phosphorylation, stabilizes SMAD3, and promotes BTG2 transcription independently of p53 status. These events culminate in G2/M cell-cycle arrest and reflect a potential SET/TAF-Iβ–PP2A–SMAD3–BTG2 signaling pathway. Our findings suggest BTG2 as both a mechanistic effector and a potential prognostic biomarker in myeloid leukemia. OBJECTIVE: This study aims to define the transcriptional consequences of FTY720-mediated disruption of the SET/TAF-Iβ–PP2A complex and to elucidate the molecular mechanism by which FTY720 induces BTG2 expression and antileukemic effects. METHODS: We performed transcriptome analyses of FTY720-treated THP-1 cells and SET/TAF-Iβ-depleted U2OS cells to identify commonly regulated genes and enriched signaling pathways. RT-qPCR, western blotting, co-immunoprecipitation, and ChIP-qPCR were conducted to validate BTG2 induction and investigate the SET/TAF-Iβ–PP2A–SMAD3 regulatory pathway. Cell-cycle effects were evaluated by assessing cyclin B1 and Cdc25C abundance and by performing cell-cycle profiling following FTY720 treatment. RESULTS: Transcriptome analysis revealed that FTY720 treatment and SET/TAF-Iβ depletion commonly upregulated BTG2, which showed the strongest induction among shared targets. FTY720 stabilized SMAD3 through ERK dephosphorylation and enhanced SMAD3 binding to the BTG2 promoter, leading to increased BTG2 transcription. Functionally, FTY720 reduced cyclin B1 and Cdc25C levels and induced G2/M arrest, consistent with BTG2-mediated cell-cycle regulation. CONCLUSION: These findings suggest that BTG2 may function as a downstream effector of FTY720-mediated SET/TAF-Iβ inhibition and indicate that a SMAD3-dependent mechanism could contribute to G2/M arrest in leukemia.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"549-558"},"PeriodicalIF":2.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146051740","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}