Background Cutaneous squamous cell carcinoma (cSCC) is the second most common form of non-melanoma skin cancer (NMSC), with a steadily increasing global incidence, especially in populations with prolonged ultraviolet (UV) exposure. Advanced or metastatic cSCC carries a poor prognosis, while the application of targeted therapies and immunotherapies remains in the exploratory stage, due to limited understanding of the underlying mechanisms of cSCC occurrence and progression. Epigenetic dysregulation plays important roles in the progression of cSCC. However, how multi-dimensional regulatory networks reshape the epigenetic landscape and contribute to dysregulated gene expression in cSCC remains unclear. Methods In this study, we performed parallel RNA m6A sequencing, 850K DNA methylation arrays, whole transcriptome sequencing, and ATAC-seq chromatin accessibility profiling on samples from normal skin, actinic keratosis (AK), and cSCC. We analyzed the regulatory networks and pathways of epigenetic modifications on gene expression. We further explored the crosstalk of epigenetic regulatory networks by correlation analysis. By integrating single-cell RNA-seq data, we identified epigenetically upregulated candidate genes and confirmed their expression and functions with experimental methods. Results Our integrated multi-omics analysis provides a comprehensive and dynamic epigenetic map of cSCC progression. Further analysis revealed that DNA methylation and m6A modification jointly regulate gene expression through independent and synergistic ways. The identified epigenetically upregulated candidate genes IDO1, IFI6, and OAS2 were validated to be overexpressed in cSCC tissues and cell lines, and functional assays confirmed their potential key roles in regulating the processes of cell proliferation, migration and invasion in cSCC. Conclusions By integrating multi-omics data, this study systematically highlights the multi-layered epigenetic alterations and regulatory mechanisms involved in cSCC development. This multi-stage, multi-omics, and multi-resolution integrated analysis provides a theoretical basis and new insights for future personalized treatment strategies for cSCC.

The sedimentary ecosystems of deep-sea floors harbor abundant biological resources, with fungi emerging as predominant eukaryotic taxa that perform crucial ecological roles. However, the adaptive strategies enabling fungal survival in these extreme low-oxygen environments remain poorly understood. We elucidated the hypoxic adaptation mechanisms of Chaetomium globosum YP-106, an oxygen-sensitive fungus isolated from 6 215-m deep seawater in Yap Trench in the western Pacific. Under hypoxic conditions, the strain growth rate was reduced with significant mycelial morphological alterations. Multi-omics analyses revealed 313 differentially abundant metabolites (DAMs) and 661 differential expression genes (DEGs), enriched in mainly fatty acid metabolism (degradation/synthesis) and carbohydrate utilization pathways. It is noteworthy that gene ontology (GO) enrichment analysis identified 171 membrane-associated genes, suggesting that structural membrane remodeling may serve as a key adaptive strategy. Integrated pathway analysis demonstrated metabolic reprogramming characterized by suppressed tricarboxylic acid (TCA) cycle activity and preferential activation of anaerobic glycolysis for ATP production. Importantly, the NADH dehydrogenase-mediated NAD+ regeneration was enhanced as a compensatory mechanism sustaining residual TCA cycle function. These findings elucidated hypoxic metabolic mechanisms in deep-sea ascomycetes, enhanced our understanding of microbial energy conservation strategies in oxygen-deprived environments, and offered novel perspectives on eukaryotic extremophile adaptation mechanisms in benthic ecosystems.

Drosha is a critical regulator of kidney development; its loss or mutation, identified in a subset of Wilms tumor (WT), a pediatric kidney cancer, leads to nephric cap mesenchyme developmental defects. Here, we investigated the role of Drosha in mesangial cells and its impact on glomerular capillary tuft formation. Mesangial cells specific deletion of Drosha (Drosha cKO) in mouse model was generated. Deletion of Drosha in mesangial cells disrupted the glomerular capillary tufts formation, leading to dysplastic glomeruli, proteinuria, oliguria, reduced looping of glomerular capillaries and capillary dilation. Drosha knockdown in mesangial cells (SV40 MES 13) leads to decreased cell proliferation and reduced Gata3 protein level. Transcriptome analysis by RNA-seq shows decreased levels of ribosomal protein genes (RPGs) but unaltered mRNA levels of major genes affecting kidney development, including Gata3, Pax2, Atn1, Wt1 etc., in Drosha-KD compared to Control SV40 MES13 cells. Further analysis indicates Drosha regulates the translation of Gata3 in mesangial cells via regulating RPG transcription. Removal of Drosha in adult mesangial cells did not cause significant kidney dysfunction, indicating that Drosha functions primarily during development rather than in homeostasis. Our work reveals that Drosha in mesangial cells orchestrates the formation of glomerular capillary tufts by regulating Gata3 translation. It identifies the critical role of DROSHA in nephric development and proposes DROSHA as a novel potential causal gene for congenital anomalies of the kidney and the urinary tract (CAKUT).

Background:Neuroblastoma is a heterogeneous pediatric tumor with variable clinical outcomes. Current prognostic markers are insufficient to predict patient survival accurately, necessitating the identification of novel biomarkers and therapeutic targets. This study aimed to develop a robust prognostic model by integrating CRISPR screening data and transcriptomic profiles, and to explore its correlation with the tumor immune microenvironment. Methods:We integrated Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screening data from the DepMap database (version 24Q2) and gene expression profiles from neuroblastoma patients to identify key genes associated with neuroblastoma prognosis. Essential genes with Computational Evaluation of RNAi Essentiality Scores (CERES) scores less than -1 in at least 80% of 34 neuroblastoma cell lines were intersected with differentially expressed genes (|logFC| >2, P<0.05) from the National Genomics Data Center (NGDC) dataset (accession code HRA002064), resulting in 43 overlapping genes. Random forest analysis and multivariate Cox regression were conducted on the GSE49710 training set (n=498) to construct a prognostic model. The model was externally validated using the E-MTAB-8248 dataset (n=223). Immune infiltration and immunotherapy response were assessed using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE), Microenvironment Cell Populations counter (MCPcounter), Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT), immunophenoscore (IPS), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. Results:A three-gene prognostic model comprising PKMYT1, CDT1, and NCAPG was established. Patients were stratified into high-risk and low-risk groups based on the median RiskScore of 9.514526. In the training set, high-risk patients exhibited significantly poorer overall survival compared to low-risk patients (log-rank test, P<0.001). The model outperformed traditional clinical factors and demonstrated consistent prognostic value in the external validation cohort. High-risk patients showed lower immune cell infiltration, higher TIDE scores, and lower IPS values, suggesting an immunosuppressive microenvironment and reduced likelihood of responding to immunotherapy. In contrast, low-risk patients had higher immune infiltration and a predicted immunotherapy response rate of 70% versus 36% in the high-risk group. Conclusions:The three-gene prognostic model effectively stratifies neuroblastoma patients by survival risk and correlates with immune microenvironment characteristics. This model has potential clinical utility for prognosis prediction and guiding personalized immunotherapy strategies in neuroblastoma.

OBJECTIVE:To assess the diagnostic value of whole exome sequencing (WES) for fetuses undergone induced abortion due to structural abnormalities. METHODS:A retrospective analysis was carried out on 43 aborted fetuses with negative results for copy number variation (CNV) testing from January 2023 to June 2024 at Northwest Women's and Children's Hospital. Trio-WES was carried out on the tissues from the aborted fetuses. This study has been approved by the Ethics Committee of the Hospital (Ethics No. 21-036). RESULTS:Among the 43 abortic fetuses, WES has detected pathogenic variants in 15 cases, with a total of 9 pathogenic variants, 5 suspected pathogenic variants, and 5 variants of uncertain significance. No definite pathogenic variants were detected in the remaining 28 cases. CONCLUSION:For fetuses with structural abnormalities and negative results from CNV testing, WES can increase the diagnostic rate and facilitate etiological diagnosis and genetic counseling.

BACKGROUND:U2AF2 (U2 small nuclear ribonucleoprotein auxiliary factor 2), a crucial spliceosome component regulating RNA splicing, plays a dual role in T-cell function and tumorigenesis. This study integrated multi-omics analysis with experimental validation to elucidate the oncogenic mechanisms of U2AF2 in colon adenocarcinoma (COAD). METHODS:U2AF2 expression and its clinical significance were analysed using publicly available COAD transcriptomic and clinical datasets. Single-cell RNA sequencing (scRNA-seq) of COAD tissues and multiplex immunofluorescence were used to assess the association between U2AF2 expression and tumour immune microenvironment composition. The in vitro functional consequences of U2AF2 knockdown on proliferation, migration, and apoptosis were evaluated in COAD cell lines (HCT116, HCT8) using specific assays. RESULTS:The results revealed that splicing factors play a key role in viral infection and regulating of T cell function in the CD4+ cell subsets. U2AF2 mRNA and protein expression were significantly upregulated in COAD patients and were strongly associated with poor prognosis. U2AF2 also exhibited high diagnostic efficiency in COAD and predicted poor overall and disease-free survival. Our study also revealed that high U2AF2 expression was significantly correlated with decreased infiltration levels in CD4+ T cells. Furthermore, U2AF2 knockdown significantly inhibited COAD cell proliferation and migration, while promoting apoptosis. CONCLUSIONS:We demonstrate U2AF2's dual oncogenic mechanisms, driving malignant transformation through aberrant RNA splicing and fostering immunosuppression by reshaping the tumour immune landscape. These findings establish U2AF2 as a promising novel therapeutic target and prognostic biomarker for COAD.

Maize (Zea mays L.), a globally significant cereal crop, is produced in vast quantities worldwide. However, its growth is severely constrained by low temperatures, particularly during seed germination, which significantly impairs seedling emergence. In this study, genetic diversity across six germination-associated phenotypic traits (RGR, RSL, RTL, RRSA, RRV, and RSVI) of 304 inbred lines was analyzed, to evaluate the capacity of these lines for low-temperature tolerance. Genome-wide association study (GWAS) was carried out by combining six germination-associated phenotypic traits and genotypic data from 30-fold resequencing. The gene ZmBARK1 was identified through integrated GWAS and RNA-seq analyses, and its association with low-temperature tolerance during maize germination was validated by quantitative real-time PCR (qRT-PCR). ZmBARK1, encoding BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1, was located on the bin 4.09 region of maize chromosome 4. Amino acid comparison and subcellular localization analyses revealed that ZmBARK1 is highly homologous to AtBAK1 and is localized to the plasma membrane of the cell, which may be involved in regulating brassinosteroid (BR) signaling. In addition, we revealed the role of ZmBARK1 in low-temperature tolerance during maize germination. Compared with wild-type (WT), the ethyl methanesulfonate (EMS) mutant zmbark1 was characterized by substantially enhanced low-temperature tolerance. Overall, these findings provide promising candidate genes, improve low-temperature tolerance in maize, and advance the understanding of regulatory mechanisms underlying maize’s response to low-temperature stress.

Plant height (PH) and ear height (EH) are closely related to dense planting characteristics and lodging resistance of maize (Zea mays L.). Increasing the planting density will lead to changes in the structural characteristics of maize plants, such as reduced stem length and stem strength, thereby influencing their yield and quality. Therefore, analyzing the genetic basis of PH and EH in maize can provide valuable information for cultivating ideal plant types with suitable PH and EH. This study aims to identify stable genomic regions and candidate genes associated with PH and EH in maize through Meta-QTL (MQTL) analysis. A total of 187 original QTLs were collected from 13 published articles on QTL localization related to maize PH and EH. A high-density consistency map with a total length of 6970.00 cM was constructed, and 152 original QTLs were successfully projected into the consistency map. The remaining 35 QTLs could not be projected onto the consistency map, which may be attributed to a lack of common markers between the original and consistency map or to the QTL exhibiting low phenotypic variance explained (PVE), resulting in large confidence intervals (CIs). Then, 29 MQTLs were identified on 10 chromosomes via meta-analysis. Among them, the three identified MQTLs, i.e., MQTL4-1, MQTL4-2, and MQTL6-1, were specifically controlled by maize EH. Further analysis achieved 188 candidate genes in all MQTL intervals, which were related to maize plant development and morphogenesis. Meanwhile, the gene ontology (GO) enrichment analysis revealed that these candidate genes were involved in 77 GO annotations. These findings thus will help us better understand the molecular genetic basis of maize PH and EH under various environments, and thereby achieve an increased yield with maize dense planting breeding.

AIM:This study aimed to study the inhibitory effect of niraparib alone or in combination with GD2 specific antibody on Bladder Cancer (BCa). METHODS:The migration ability of BCa cells was assessed through a scratch assay. CCK-8 assay was performed to evaluate the viability of BCa cells, and Transwell invasion assays were utilized to examine invasive capacity. The expression levels of E-cadherin and vimentin in BCa cells were measured using QRT-PCR. RESULTS:Western blot showed the EMT level to be the lowest in the niraparib+GD2 group. The transwell invasion assay suggested that the invasion ability of BCa cells was weakened in the niraparib+ GD2 group. CCK8 assay indicated that the proliferation ability of BCa cells was decreased. Scratch test suggested that the migration ability of BCa cells was weakened. PCR result showed that the niraparib + GD2 group had the most significant inhibitory effect on mRNA expression of EMT markers. CONCLUSION:Niraparib combined with a GD2-specific antibody exerted a more prominent inhibitory effect on BCa.

BackgroundCinnamoyl-CoA reductase (CCR) catalyzes the first step in lignin biosynthesis and is crucial for plant development and stress response. Although CCR genes are characterized in many plants, a complete analysis of the soybean CCR family and its response to abiotic stress is limited.MethodsWe identified soybean CCR genes genome-wide using bioinformatics. Phylogenetics, gene structures, motifs, chromosomal distribution, and synteny were analyzed. Promoter regions were checked for cis elements. Expression patterns were studied across tissues and under four abiotic stresses (salt, alkaline, drought, and osmotic) using transcriptome data.ResultsFifteen CCR genes (GmCCR1-GmCCR15) were identified in the soybean genome, distributed across 12 chromosomes. Phylogenetic analysis revealed two major subfamilies with distinct evolutionary origins. The genes encode proteins ranging from 269 to 363 amino acids, with predicted subcellular localization mainly in the Golgi apparatus. Motif analysis identified 10 conserved domains, showing subfamily-specific distribution patterns. Promoter analysis uncovered abundant hormone-responsive and stress-related cis-elements, including abscisic acid response elements (ABRE), methyl jasmonate-responsive elements, and drought-responsive elements. Transcriptome analysis demonstrated tissue-specific expression patterns, with higher levels in roots, stems, and developing seeds. Under abiotic stress conditions, five genes (GmCCR1, GmCCR4, GmCCR7, GmCCR8, and GmCCR15) were significantly upregulated, while three genes (GmCCR2, GmCCR11, and GmCCR13) were downregulated or showed no response. Notably, GmCCR4 exhibited the most dramatic changes in expression across all stress treatments, with peak upregulation occurring 3 hours post-treatment.ConclusionsThis analysis explores soybean CCR gene evolution, structure, and divergence. Identifying stress-responsive CCR genes, especially GmCCR4, highlights a target for improving soybean stress tolerance via molecular breeding or genetic engineering. These findings enhance understanding of lignin regulation under stress and support the development of climate-resilient soybeans.

Tumor-associated macrophages (TAMs) play dual roles in cancer, either promoting or suppressing tumor progression, complicating therapeutic approaches. TAMs include recruited macrophages (recMacs), derived from circulating monocytes, and tissue-resident interstitial macrophages (IMs). We recently identified a heterogeneous population of chemokine-expressing IMs, including subsets that support tertiary lymphoid structure (TLS) formation during lung inflammation. Here, we show that IMs can be either pro- or anti-tumorigenic, depending on the subset. Using Pf4 Cx3cr1 mice to deplete CD206hi IMs expressing Cxcl13, Cxcl9, and Cxcl10, we demonstrate their essential role in TLS formation, lymphocyte recruitment, and tumor suppression in melanoma and lung adenocarcinoma. In contrast, Ccl2-expressing IMs promote tumor growth by recruiting pro-tumorigenic recMacs. Spatial transcriptomics confirmed the distinct localization and chemokine profiles of these subsets. Finally, CCR5 blockade with the FDA-approved inhibitor Maraviroc during neoantigen vaccination improved tumor control by preventing the migration of immunosuppressive, antigen-presenting recMacs (moDCs). These findings support the development of macrophage-targeted therapies by identifying pro-tumorigenic subsets and recMac trafficking as actionable targets, while preserving macrophage populations that sustain anti-tumor immunity.

Mesenchymal stem cells (MSCs), being multipotent progenitors, have received the most widespread regulatory approval for commercialization as off-the-shelf cell therapies. Understanding the key molecular mechanisms regulating MSC differentiation is crucial for advancing their clinical utilization. Drosha is a critical enzyme in miRNA biogenesis. Despite its established role in diverse physiological processes, the involvement of Drosha in the adipogenic differentiation of MSCs has not been previously characterized. Here the role of Drosha/microRNA pathway in regulating the adipogenesis of OP9, a MSC derived from mouse bone marrow stroma, is characterized. Knocking down Drosha in OP9 significantly reduced its adipogenic capacity. Small RNA-seq analysis revealed that miR-204 and miR-15b were significantly downregulated in the adipogenic process of OP9 cells upon Drosha removal. Further exploration showed that the activity of ERK1/2, which has been shown to be able to suppress the transcriptional activity of PPARγ, was significantly increased in Drosha KO OP9 cells. Introducing miR-204 or miR-15b into OP9 cells significantly enhanced their adipogenic capacity and partially rescued the adipogenic defects caused by Drosha knockout. Mechanistically, miR-15b regulates ERK mediated adipogenic differentiation via repressing NRP2. Our data demonstrate that the Drosha/miR-15/NRP2 axis regulates adipogenesis of MSCs by modulating the ERK/PPARγ pathway. This discovery unveils a previously unappreciated molecular mechanism governing MSC adipogenic differentiation and suggests new avenues for exploring the therapeutic potential of MSCs.

BackgroundTamoxifen is an effective treatment for hormone receptor-positive breast cancer (BC). Despite its effectiveness, there have been many reports of adverse reaction. However, the relationship between Tamoxifen-related adverse events (ADEs) and patient age remains unclear.AimTo enhance clinical medication guidance and drug safety by identifying age-specific ADEs associated with Tamoxifen therapy in female breast cancer patients, thereby offering a more robust foundation for evidence-based clinical practice.MethodsADEs reports of Tamoxifen from the FAERS database were extracted from the first quarter of 2004 to the second quarter of 2023. Reporting odds ratio (ROR) data analysis strategy was used for mining signal strength that represents age differences in ADEs related to Tamoxifen.ResultsThe number of efficient ADE signals associated with Tamoxifen for female BC included in the analysis was 338 in premenopausal women, 847 in perimenopause and 1525 in postmenopause respectively. Our study showed age differences in three age groups of ADEs with Tamoxifen in female BC. Perimenopausal and postmenopausal women receiving tamoxifen therapy demonstrated a significantly higher incidence of adverse drug reactions, particularly involving the gastrointestinal tract, renal/urinary systems, hematologic/lymphatic systems, endocrine functions, and immune responses. It was particularly concerned that ADEs associated with ear and labyrinth disorders had only been reported in perimenopause.ConclusionAge differences was detected in ADE signals related to Tamoxifen. There were significant differences in Tamoxifen related ADEs of premenopausal, perimenopausal and postmenopausal women with BC in different systems. To ensure the safety of medicines, we should be aware of the age-related differences in ADEs and take appropriate preventive measures to reduce incidence of serious ADEs.

The KCTD gene family is conserved across species, yet the knowledge of its function is limited. Recently, increasing studies focused on KCTD5 emerged. The functions of KCTD5 and its associations with various diseases were revealed. However, the function of KCTD5 in vivo has remained elusive. We generated Kctd5+/- mice with the Kctd5 gene's exon 2 deleted using CRISPR/Cas9 technology. Breeding experiments on Kctd5+/- mice showed that only Kctd5+/- and Kctd5+/+ mice could be born normally, while Kctd5-/- embryos died in early embryonic development. Compared to Kctd5+/+ mice, Kctd5+/- mice have a shorter lifespan and exhibit spleen enlargement, abnormal blood cell counts, and metabolic disorders, including elevated cholesterol and triglyceride levels. Genome-wide gene expression analysis revealed that KCTD5 may affect the PPAR signaling pathway and subsequent the expression of Apo family genes, thereby regulating lipid metabolism. In summary, our study identified a previously unrecognized role of KCTD5 in regulating lipid metabolism and KCTD5 deficiency-induced animal phenotype, and revealed multiple correlations between KCTD5 and various molecules in mice.

Aims The RNA-binding protein LSM7 is essential for RNA splicing, acting as a key component of the spliceosome complex; however, its specific role in breast cancer (BC) has not been extensively investigated. Materials and methods LSM7 expression in BC samples was evaluated through bioinformatics analysis and immunohistochemistry. The impact of LSM7 on promoting metastatic tumor characteristics was examined using transwell and wound healing assays, as well as an orthotopic xenograft model. Additionally, the involvement of LSM7 in alternative splicing of CD44 was explored via RNA immunoprecipitation and third-generation sequencing. The regulatory role of TCF3 in modulating LSM7 gene expression was further elucidated using luciferase reporter assays and chromatin immunoprecipitation. Key findings Our findings demonstrate that LSM7 was significantly overexpressed in metastatic BC tissues and was associated with poor prognostic outcomes in patients with BC. LSM7 overexpression markedly increased the migratory and invasive capabilities of BC cells in vitro and significantly promoted spontaneous lung metastasis in vivo. Furthermore, RIP-seq analysis revealed that LSM7 binded to CD44 RNA, enhancing the expression of its alternatively spliced isoform CD44s, thereby driving BC metastasis and invasion. Additionally, the transcription factor TCF3 was found to activate LSM7 transcription by directly binding to its promoter. Significance In summary, this study highlights the pivotal role of LSM7 in the production of the CD44s isoform and the promotion of breast cancer metastasis. Targeting the TCF3/LSM7/CD44s axis may offer a promising therapeutic strategy for breast cancer treatment.

MCPH1 has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of Mcph1 in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of Mcph1 resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as Satb2 and Cdkn1c, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized Mcph1 knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in Mcph1 knockout MEFs, and silencing p19Arf restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.

Purpose Resistance to tamoxifen poses a significant clinical challenge in the management of Luminal B breast cancer, necessitating the identification of novel biomarkers for predicting treatment response and prognosis. The specific role of DYNLT1 in endocrine response within Luminal B breast cancer remains uncertain. Methods The expression levels of DYNLT1 were assessed in breast cancer samples using immunohistochemistry, real-time PCR, and western blot analysis. The potential role of DYNLT1 in promoting resistance to tamoxifen was investigated through cell viability and colony formation assays. Furthermore, an in vivo mammary fat pad model was employed to examine the impact of DYNLT1 on tamoxifen resistance in breast tumors. Additionally, luciferase activity assays were conducted to explore the activation of the ER signaling pathway. The enrichment of ELAVL1 on mRNA of DYNLT1 was detected utilizing RNA immunoprecipitation assay. Results This study demonstrated that the DYNLT1 expression was particularly upregulated in the Luminal B subtype of breast cancer tissues. Notably, elevated DYNLT1 expression was associated with poorer relapse-free survival among Luminal B breast cancer patients treated with tamoxifen. Functionally, increased DYNLT1 expression induced resistance to tamoxifen both in vivo and in vitro. Additionally, upregulation of DYNLT1 significantly promoted ligand-independent activation of the ER signaling pathway. ELAVL1-mediated m6A modification led to overexpression of DYNLT1 and facilitated the acquisition of tamoxifen resistance phenotype. Conclusion Overall, these findings highlight that DYNLT1 could potentially act as a novel biological marker for predicting the effectiveness of tamoxifen treatment and patient prognosis in Luminal B breast cancer.

The root is an important organ by which plants directly sense variation in soil moisture. The discovery of drought stress-responsive genes in roots is very important for the improvement of drought tolerance in wheat varieties via molecular approaches. In this study, transcriptome sequencing was conducted on the roots of drought-tolerant wheat cultivar YH1818 seedlings at 0, 2, and 7 days after treatment (DAT). Based on a weighted gene correlation network analysis of differentially expressed genes (DEGs), 14 coexpression modules were identified, of which five modules comprising 3107 DEGs were related to 2 or 7 DAT under drought stress conditions. A total of 223,357 single-nucleotide polymorphisms (SNPs) of these DEGs were retrieved from public databases. Using the R language package and GAPIT program, association analysis was performed between the 223,357 SNPs and the drought tolerance coefficient (DTC) values of six drought resistance-related traits in 114 wheat germplasms. The results revealed that 18 high-confidence SNPs of 10 DEGs, including TaPK, TaRFP, TaMCO, TaPOD, TaC3H-ZF, TaGRP, TaDHODH, TaPPDK, TaLectin, and TaARF7-A, were associated with drought tolerance. The RT-qPCR results confirmed that these genes were significantly upregulated by drought stress at 7 DAT. Among them, TaARF7-A contained three DTC-related SNPs, which presented two haplotypes in the tested wheat germplasms. YH1818 belongs to the Hap1 allele, which is involved in increased drought tolerance. This study revealed key modules and candidate genes for understanding the drought-stress response mechanism in wheat roots.