Mol. Genet. Genomics [JOURNAL]
Sun
200 papers
Contribution of FXR1 genetic polymorphisms to breast cancer susceptibility in Chinese females.
Zhang C, Zhang G, Fida S … +4 more , Zhang Y, Wang S, Zhang Z, Song C
Mol Genet Genomics · 2026 May · PMID 42138731 · Publisher ↗
Fragile X-related protein 1 (FXR1) is an mA-binding protein that plays a critical role in cancer development and progression. It has unclear associations between its genetic variants and breast cancer (BC) susceptibility...
Fragile X-related protein 1 (FXR1) is an mA-binding protein that plays a critical role in cancer development and progression. It has unclear associations between its genetic variants and breast cancer (BC) susceptibility. This study explored correlations of FXR1 single nucleotide polymorphisms (SNPs) with BC susceptibility. A frequency matching case-control study included 802 histologically confirmed BC cases and 802 age-matched controls (± 2 years) of Han-Chinese ethnicity. Four FXR1 SNPs were selected using bioinformatics. Associations with BC risk and reproductive factor interactions were assessed using conditional logistic regression. FXR1 expression was evaluated by quantitative real-time PCR (qRT-PCR), with RNA structural and miRNA-binding changes predicting using RNAfold and miRNASNP. The mA-related target genes were identified by QTLbase and RMBase. Tissue expression analyzed via GEPIA. The FXR1 rs2601 A > G variant was significantly associated with reduced BC risk, confirmed by stratification. For rs2601, the said polymorphism exhibited association with the reduced incidence with BC in specific subgroups of studied cohort when comparison was conducted between homozygous wild type AA and AG + GG genotypes. Haplotype analysis revealed the haplotype AAAT and TAGT is probably protective to the incidence of BC in this population. Additionally, a significant additive interaction was observed between rs2601 and age at menarche. qRT-PCR showed genotype-dependent FXR1 expression. Integrative analysis identified 10 candidate associated genes, among which CCDC39 was downregulated in BC tissues(P < 0.01). The FXR1 rs2601 A > G is probably protective to BC among Han Chinese women and it has an interaction with reproductive factors. This could provide theoretical basis for BC screening and prevention.
The antibacterial activity and plant growth-promoting potential of Streptomyces lopnurensis TRM49590 based on whole-genome mining.
Lu J, Yuan J, Xue S … +4 more , Zhang R, Zhu Y, Gong S, Zheng B
Mol Genet Genomics · 2026 May · PMID 42138723 · Publisher ↗
The Streptomyces lopnurensis TRM49590, isolated from the sedimentary deposits of Lop Nur, Xinjiang, China, thrives in an extreme environment marked by high salinity and intense radiation. This unique habitat endows it wi...
The Streptomyces lopnurensis TRM49590, isolated from the sedimentary deposits of Lop Nur, Xinjiang, China, thrives in an extreme environment marked by high salinity and intense radiation. This unique habitat endows it with a high potential for producing novel and bioactive secondary metabolites. This study explored its growth-promoting characteristics and the antimicrobial activity against the plant disease pathogens based on whole-genome mining. The whole-genome annotation revealed an abundance of gene clusters associated with plant growth promotion and environmental adaptation in S. lopnurensis TRM49590. A total of 24 active secondary metabolite Bio-synthetic Gene Clusters (smBGCs) capable of synthesizing known or novel compounds were identified using antiSMASH 8.0 and BAGEL 4. These findings suggest the potential of S. lopnurensis TRM49590 to produce novel secondary metabolites with both antimicrobial and herbicidal activities. Furthermore, S. lopnurensis TRM49590 exhibits capabilities in nitrogen fixation, potassium solubilization, and the secretion of multiple extracellular enzymes, significant inhibitory effects on Fusarium oxysporum f. sp. Vasinfectum ATCC 31083 and Verticillium dahliae ATCC 36211, further substantiating its potential in promoting plant growth and enhancing plant resistance. This study provides the necessary theoretical basis for the development and practical application of S. lopnurensis TRM49590.
Comparison between a conventional tool and deep learning models for RNA velocity analysis of scRNA-Seq data.
Sauda MR, Rodrigues AB, de Oliveira Lyra ML … +4 more , Grotto RMT, Gu L, de Campos Melo T, Valente GT
Mol Genet Genomics · 2026 May · PMID 42126634 · Full text
Single-cell RNA sequencing (scRNA-Seq) enables analysis of gene expression at single-cell resolution. RNA velocity analysis infers the temporal dynamics of transcriptional states from the relative abundances of spliced/u...
Single-cell RNA sequencing (scRNA-Seq) enables analysis of gene expression at single-cell resolution. RNA velocity analysis infers the temporal dynamics of transcriptional states from the relative abundances of spliced/unspliced mRNA quantified via scRNA-Seq. Classical RNA velocity approaches, such as scVelo, implement gene-specific kinetic modeling. Deep learning methods including DeepVelo, VeloVI, LatentVelo, SymVelo, and scTour are based on variational autoencoders (VAEs), which allow to enhance the robustness and accuracy by leveraging nonlinear latent representations. Here, we systematically evaluated the performance of deep learning RNA velocity tools by comparing with the scVelo dynamical model to access the possible advantages of VAE-base methods. For this purpose, public datasets (GSE149689 and GSE203233) were initially processed using a standard scRNA-Seq pipeline. Comparisons among results of selected velocity tools were conducted using cosine similarity of velocity vectors to assess directional concordance, and by mean squared error analysis of trajectory continuity for the deep learning models. Overall, VAE methods produced significant, richer, and more directionally coherent and consistent velocity fields than the classical model. Our findings indicate that deep learning models provide more consistent and biologically plausible cell-state trajectories, although at the expense of higher computational demands and reliance on accurate splicing quantification. Altogether, our results underscore the relevance of VAE-based frameworks to advance RNA velocity analysis while highlighting the need for careful preprocessing.
UPF1 promotes wound healing in diabetic foot ulcer by reducing CYP1A1-induced oxidative stress through enhancing EGR1 degradation.
Qiu ZY, Ma YL, Zhang YX … +5 more , Fu J, Xu WC, Kuang SJ, Xu JQ, Liang ZH
Mol Genet Genomics · 2026 May · PMID 42095912 · Publisher ↗
Diabetic foot ulcer (DFU) is a severe and debilitating complication of diabetes with limited effective therapeutic strategies, and persistent oxidative stress and inflammation are the core pathological factors leading to...
Diabetic foot ulcer (DFU) is a severe and debilitating complication of diabetes with limited effective therapeutic strategies, and persistent oxidative stress and inflammation are the core pathological factors leading to its impaired wound healing. RNA-binding protein UP frameshift 1 (UPF1) is implicated in modulating oxidative stress pathways, yet its regulatory role and underlying mechanism in DFU-associated oxidative stress remain largely unelucidated. This study aims to explore the function of UPF1 in oxidative stress during DFU pathogenesis and identify its related molecular regulatory axis, so as to provide novel therapeutic targets for DFU management. Human dermal fibroblasts (HDFs) were exposed to 30 mM high glucose (HG) to simulate diabetic conditions. The results showed that HG stimulation increased cytochrome P450 family 1 subfamily A member 1 (CYP1A1) and early growth response 1 (EGR1) expression, exacerbating oxidative stress and inflammation in HDFs. EGR1 knockdown or CYP1A1 inhibition attenuated these effects. Mechanistically, EGR1 transcriptionally activated CYP1A1, while UPF1 bound to and destabilized EGR1 mRNA. As expected, UPF1 upregulation rescued HG-induced inflammation and oxidative stress in HDFs, whereas concurrent EGR1 overexpression abolished this protective effect. In conclusion, UPF1 exerts a protective role in HG-stressed HDFs by degrading EGR1 mRNA, which in turn suppresses the transcriptional activation of CYP1A1 and subsequent CYP1A1-mediated oxidative stress and inflammation, thus uncovering a novel UPF1-EGR1-CYP1A1 regulatory axis in DFU pathogenesis. These core findings not only enrich the molecular understanding of oxidative stress regulation in DFU but also provide promising novel therapeutic targets for DFU management.
SETDB1 induces H3K9me3 methylation modification of RASSF2 to inhibit PTEN and facilitate ovarian cancer progression.
Wang J, Li X, Chang J … +5 more , Hou X, Sun L, Yan Y, Shu L, Wu X
Mol Genet Genomics · 2026 May · PMID 42095894 · Publisher ↗
Ovarian cancer (OV) is one of the deadliest gynecological malignancies, and its high heterogeneity significantly impacts treatment efficacy. Against this background, the molecular mechanisms underlying the pathogenesis o...
Ovarian cancer (OV) is one of the deadliest gynecological malignancies, and its high heterogeneity significantly impacts treatment efficacy. Against this background, the molecular mechanisms underlying the pathogenesis of this lethal disease have attracted extensive research attention. However, the pathogenic mechanisms of OV remain incompletely understood. Therefore, this study systematically investigates the pathogenesis of OV. This study collected 20 paired clinical samples comprising OV tissues and benign ovarian tissues to investigate RASSF2 expression. The biological effects of RASSF2 were investigated using both in vitro and in vivo models, including assessments of proliferation and migration. The impact of RASSF2 on PTEN protein stability was examined through co-immunoprecipitation and cycloheximide (CHX) chase assays. Additionally, chromatin immunoprecipitation (ChIP) was performed to investigate the SETDB1/RASSF2 interaction and H3K9me3 modifications on the chromatin of RASSF2. OV tissues exhibited significantly lower RASSF2 expression compared to normal tissues, and this reduction was associated with poorer patient survival. Overexpression of RASSF2 inhibited the proliferation and migration of OV cells. Additionally, RASSF2 inhibited OV growth in vivo. Mechanistically, RASSF2 stabilized PTEN expression to inhibit the activation of PI3K/AKT pathway. In addition, SETDB1 drove OV progression by increasing H3K9me3 enrichment at the RASSF2 promoter to negatively regulate RASSF2 expression. H3K9me3‑modified RASSF2 promotes ovarian cancer metastasis by regulating PTEN expression, which may offer a potential therapeutic target to counteract distant dissemination of OV.
Exosomal miR-27a-3p promotes osteosarcoma lung metastasis by negatively regulating TNFAIP3 to form a premetastatic niche.
Jiang Y, Fan C, Tan Q … +7 more , Wang Y, Xu J, Zuo X, Li X, Wu X, Ma J, Yan L
Mol Genet Genomics · 2026 May · PMID 42095873 · Publisher ↗
Osteosarcoma (OS) is a highly aggressive primary bone malignancy with a strong predilection for lung metastasis, and the formation of a lung pre-metastatic niche represents a key early event driving OS distant disseminat...
Osteosarcoma (OS) is a highly aggressive primary bone malignancy with a strong predilection for lung metastasis, and the formation of a lung pre-metastatic niche represents a key early event driving OS distant dissemination. Elucidating the molecular mechanisms of pre-metastatic niche establishment is therefore critical for developing novel anti-metastatic therapies for OS. However, the mechanisms by which OS cells initiate the formation of a lung pre-metastatic niche remain poorly understood. Exosomes, as key mediators of intercellular communication, play a pivotal role in promoting tumor metastasis by shuttling functional biomolecules to remodel the microenvironment of distant target organs. In this study, we found that MG63 OS cells secreted exosomal miR-27a-3p, which targeted TNFAIP3 in lung fibroblasts, resulting in decreased TNFAIP3 protein expression. This downregulation enhanced the metastatic potential of OS cells toward lung fibroblasts. TNFAIP3 was identified as a direct target of miR-27a-3p, and TNFAIP3-Mut abrogated the regulatory effect of miR-27a-3p on TNFAIP3 expression, confirming the specific targeting relationship. Mechanistically, miR-27a-3p-mediated suppression of TNFAIP3 abrogated its negative regulation of the NF-κB pathway, leading to increased transcription of downstream inflammatory cytokines IL-1β, IL-6, and IL-8. The resulting pro-inflammatory microenvironment contributed to the establishment of a lung pre-metastatic niche, thereby promoting OS lung metastasis. These findings underscore the critical role of OS-derived exosomes in lung metastasis and suggest that exosomal miR-27a-3p may serve as a promising therapeutic target in OS lung metastasis.
Assembled and annotated reference genome and demographic history of the eastern chipmunk (Tamias striatus).
Shifflett SA, Weyer E, MacDonald ML … +1 more , Ellis VA
Mol Genet Genomics · 2026 May · PMID 42068383 · Full text
The eastern chipmunk (Tamias striatus) is an abundant North American sciurid rodent and the only extant member of the subgenus Tamias. Despite its abundance, a reference genome has not been produced for this species. Her...
The eastern chipmunk (Tamias striatus) is an abundant North American sciurid rodent and the only extant member of the subgenus Tamias. Despite its abundance, a reference genome has not been produced for this species. Here we present an assembled and annotated reference genome for the eastern chipmunk using PacBio HiFi long read sequencing data. We sequenced the genome of a vouchered male eastern chipmunk collected in Maine and stored at the National Museum. We compared the eastern chipmunk's genome with the genome of the Siberian chipmunk (Tamias sibiricus; subgenus Eutamias), the only other species in the Tamias genus with an annotated reference genome. The genomes were similar with 55.45% of genes showing collinearity and chromosomal rearrangements only occurring between chromosomes 4 and 8. We identified 219 genes under positive selection in the eastern chipmunk relative to the Siberian chipmunk. A coalescent analysis inferred the effective population size of the Maine eastern chipmunk may have steadily decreased through the Pleistocene epoch, consistent with a reduction in available habitat. We also generated short-read Illumina sequencing data from two additional eastern chipmunks collected in New Castle County, Delaware and Carbon County, Pennsylvania. We calculated nucleotide diversity over 10 kb windows across the genome (mean = 0.0014 ± 0.0012 s.d.) and identified genes with high nucleotide diversity. The eastern chipmunk reference genome will facilitate future population genetic and evolutionary studies including those investigating its role as a reservoir host for the bacterium that causes Lyme disease.
Neuroprotective role of Curcuma amada evidenced from pesticide-induced stressed Drosophila melanogaster: insights from RNAseq and gut microbiome analyses.
Bindal N, Mohanty S
Mol Genet Genomics · 2026 May · PMID 42067720 · Publisher ↗
Prolonged exposure to pesticides is linked to neurodegenerative disorders through mechanisms involving oxidative stress, inflammation, and neuronal signaling. Therapeutic plants may offer a promising and natural alternat...
Prolonged exposure to pesticides is linked to neurodegenerative disorders through mechanisms involving oxidative stress, inflammation, and neuronal signaling. Therapeutic plants may offer a promising and natural alternative for protecting against such damage. Hence, the present study aims to understand the role of Curcuma amada in mitigating pesticide-induced neurotoxicity and its molecular mechanism in Drosophila. The pesticidal stress was induced in Drosophila through oral feed of ethion and its action was confirmed through behavioural assay. The stressed flies were treated with C. amada rhizome and the effect of both ethion and ethion + C. amada was assessed through RNA profiling and gut microbiome analysis. Decrease in locomotory activity on exposure to ethion represents the induced neuronal stress and an increase was seen after C. amada was fed to the stressed flies. Many DEGs were identified through RNAseq results of stressed and C. amada treated which were further analysed using Cytoscape. In ethion and ethion + C. amada treated flies, the upregulated and downregulated genes were found to be associated with neuronal signal processing and mitochondrial function [MRPs, Dop2R, 5-HT1A, aminoacyl-tRNA synthetase (AARs), ND-B17]. A significant change in the gut microbial population (especially decrease in Lactiplantibacillus species) was observed in stressed flies. But the restoration of healthy bacterial population such as Lactiplantibacillus in C. amada treated flies evidencing the crucial role of gut microbiome in neuronal health. This study highlights the beneficial effects of C. amada from pesticidal stress which needs to be further researched to understand the underlying molecular mechanisms.
Focus on M2-TAMs and gastric cancer: a Mendelian randomization and bioinformatics analysis.
Min G, Tang H, Min G … +1 more , Li Y
Mol Genet Genomics · 2026 May · PMID 42067686 · Publisher ↗
Gastric cancer (GC), a highly aggressive and heterogeneous malignancy, remains challenging in immunotherapy despite recent advancements. This study aims to identify novel biomarkers and construct a prognostic model to im...
Gastric cancer (GC), a highly aggressive and heterogeneous malignancy, remains challenging in immunotherapy despite recent advancements. This study aims to identify novel biomarkers and construct a prognostic model to improve outcome prediction and therapeutic strategies. Mendelian randomization (MR) analysis identified immune cell subtypes linked to GC using FinnGen and GWAS cohorts. CIBERSORT and WGCNA algorithms were applied to define M2 tumor-associated macrophage (TAM)-related gene modules. Key prognostic genes were selected via Lasso-Cox regression to establish a risk model, validated using GEO datasets. Biological function disparities, tumor microenvironment heterogeneity, and therapeutic sensitivities were assessed via GSEA and immune infiltration analysis. Protein-level validation was performed using TCGA, HPA, and Western blot. MR analysis revealed 26 immune cell subtypes associated with GC. WGCNA identified 20 gene modules, with the most M2 TAM-correlated module prioritized. A prognostic signature incorporating SEC61G, BGN, and STC1 was developed, stratifying patients into distinct risk groups with divergent survival outcomes (1-/3-/5-year, all P < 0.05). High-risk patients exhibited enriched calcium signaling pathways, reduced immunotherapy responsiveness, and increased sensitivity to veriparib and palbociclib. Protein overexpression of key genes was validated in GC tissues. This integrated bioinformatics-MR framework establishes a TAM-driven prognostic model for GC, demonstrating clinical utility in survival prediction, immunotherapy efficacy evaluation, and personalized therapeutic targeting. The findings provide actionable insights for advancing precision immunotherapy in GC.
Targeting WWP1 ameliorates osteoarthritis by suppressing KLF15 ubiquitination to restore mtDNA and mitochondrial function.
Li Z, Lan W, Luo Y … +3 more , Liu P, Li X, Li H
Mol Genet Genomics · 2026 Apr · PMID 42029952 · Publisher ↗
Osteoarthritis (OA), the most prevalent chronic joint disease and a leading cause of disability, is mechanistically linked to mitochondrial dysfunction in its pathogenesis. This study aimed to elucidate the regulatory ro...
Osteoarthritis (OA), the most prevalent chronic joint disease and a leading cause of disability, is mechanistically linked to mitochondrial dysfunction in its pathogenesis. This study aimed to elucidate the regulatory role and therapeutic potential of the WWP1/KLF15/TFAM signaling axis in OA-associated mitochondrial impairment. We demonstrate that in OA chondrocytes, the E3 ubiquitin protein ligase 1 (WWP1) promotes ubiquitination and degradation of the transcription factor KLF15, reducing its protein stability. The krüppel-like factor 15 (KLF15) directly binds to the promoter of the mitochondrial transcription factor A (TFAM) and activates its transcription. Under OA conditions, TFAM expression is downregulated; restoring TFAM expression significantly enhances mitochondrial DNA (mtDNA) transcription and replication, upregulates mitochondrial-encoded genes, repairs mitochondrial membrane potential (ΔΨm), and reduces superoxide levels, thereby improving mitochondrial function and reversing metabolic dysregulation in chondrocytes. In conclusion, our findings reveal that WWP1 impairs mtDNA biogenesis by mediating KLF15 ubiquitination and degradation, leading to suppressed TFAM transcription. This results in reduced expression of mitochondrial-encoded genes and mitochondrial dysfunction, which collectively exacerbate OA pathogenesis. These insights identify the WWP1/KLF15/TFAM axis as a promising therapeutic target for OA.
XAF1 nonsense mutation rs117407731 enhances lung adenocarcinoma susceptibility via apoptosis suppression.
Xu G, Zhang H, Zhang S … +1 more , Yu D
Mol Genet Genomics · 2026 Apr · PMID 42029946 · Publisher ↗
Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, the leading cause of global cancer-related mortality. Genetic mutations play critical roles in LUAD pathogenesis. This study aims to investigate th...
Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, the leading cause of global cancer-related mortality. Genetic mutations play critical roles in LUAD pathogenesis. This study aims to investigate the role of XIAP-associated factor 1 (XAF1) rs117407731, a nonsense mutation in certain splice variants (p.22W>*, TGG to TGA), in LUAD susceptibility and cellular function. Genotyping of XAF1 rs117407731 was conducted using blood samples of 103 LUAD patients and 229 healthy individuals. Multivariate logistic regression analysis was carried out to identify independent factors associated with LUAD risk. Immunofluorescence staining showed the expression of XAF1 and XIAP in LUAD tissues. TUNEL staining was employed for cell apoptosis analysis in patient LUAD tissues or mouse tumors. A549 cells were transduced with lentiviral vectors carrying wild-type or mutant XAF1 (XAF1-WT or XAF1-MUT) for functional experiments. XAF1 rs117407731 significantly increased susceptibility to LUAD. XAF1 protein expression was reduced, XIAP expression was elevated, and cell apoptosis was decreased in LUAD tissues from rs117407731 carriers. Overexpressing XAF1-MUT abated XAF1-mediated impairment of A549 cell proliferation and enhancement of apoptosis in vitro. XAF1-MUT overexpression impaired tumor suppression in the xenograft mouse model. XAF1 rs117407731 contributes to LUAD risk by impairing XAF1-mediated apoptosis.
A novel dynamic part-wise direct and complementary template matching approach for DNA sequence similarity identification.
Uddin M, Islam MK, Hassan MR … +2 more , Ratna AS, Jahan F
Mol Genet Genomics · 2026 Apr · PMID 42029782 · Publisher ↗
Understanding DNA sequence similarity is essential for uncovering evolutionary relationships and functional insights across diverse biological systems, particularly in the era of rapidly expanding genomic data, DNA seque...
Understanding DNA sequence similarity is essential for uncovering evolutionary relationships and functional insights across diverse biological systems, particularly in the era of rapidly expanding genomic data, DNA sequence similarity analysis plays a central role in comparative genomics, evolutionary biology, and phylogenetic reconstruction. However, the rapid expansion of genomic databases has made large-scale sequence comparison increasingly challenging for traditional alignment-based approaches due to their high computational cost and limited efficiency for highly divergent sequences. Alignment-free methods provide an attractive alternative, but many existing techniques still face limitations in phylogenetic accuracy and computational efficiency. In this study, we propose a novel alignment-free method for DNA sequence similarity analysis based on dynamic template matching and subsequence similarity representation. The approach generates a sub-sequence similarity score number (SSSN) vector using direct and complementary nucleotide matching and reconstructs phylogenetic relationships from the resulting feature vectors. The method was evaluated using two benchmark datasets and four standard biological datasets. Experimental results show that the proposed approach achieves high phylogenetic accuracy (95–100%) while significantly reducing computational requirements. In particular, it is 55–1747 times faster than the MEGA tool and requires 30–99% less memory than several existing approaches. Overall, the proposed method provides an efficient and scalable framework for DNA sequence similarity analysis and phylogenetic inference in large genomic datasets. These findings demonstrate that the proposed method provides an accurate and computationally efficient framework for large-scale DNA sequence analysis, with strong potential for applications in comparative genomics, evolutionary studies, and future high-throughput genomic research. The datasets and source code supporting this study are publicly available at the provided https://github.com/machbah/DPTM_Seq_Sim Github repository.
PTK6 suppresses NSCLC ferroptosis by promoting m6A-YTHDF2-dependent FOXO3 mRNA degradation through phosphorylation.
Zhen S, Zhu Q, Wu X … +4 more , Xiong F, Ma W, Wang Z, Bo W
Mol Genet Genomics · 2026 Apr · PMID 42029771 · Publisher ↗
Ferroptosis has emerged as a potential therapeutic target for non-small cell lung cancer (NSCLC), but its regulatory mechanisms remain elusive. Protein tyrosine kinase 6 (PTK6) is overexpressed in NSCLC and linked to poo...
Ferroptosis has emerged as a potential therapeutic target for non-small cell lung cancer (NSCLC), but its regulatory mechanisms remain elusive. Protein tyrosine kinase 6 (PTK6) is overexpressed in NSCLC and linked to poor prognosis, though its role in ferroptosis is unknown. CCK-8 assay was performed to assess cell viability. Intracellular Fe2+ level was measured using an iron assay kit. Lipid peroxidation was evaluated using the C11 BODIPY probe. Dual-luciferase reporter and ChIP assays were employed to investigate FOXO3’s interaction with the APOL3 promoter. PTK6-YTHDF2 interaction was examined using Co-IP assay, and YTHDF2-FOXO3 interaction was detected using RIP assay. PTK6 knockdown exacerbated Erastin-induced ferroptosis in NSCLC cells. Mechanistically, PTK6 enhanced YTHDF2-mediated FOXO3 mRNA degradation by phosphorylating YTHDF2. FOXO3 silencing reversed PTK6 depletion’s pro-ferroptotic effects. FOXO3 transcriptionally activated APOL3 expression. APOL3 knockdown negated PTK6 silencing-driven ferroptosis sensitization. PTK6 inhibited NSCLC cells ferroptosis by promoting m6A-YTHDF2-dependent FOXO3 mRNA degradation through phosphorylating YTHDF2, thereby suppressing FOXO3-mediated APOL3 transcriptional activation.
Pangenomic and functional domain comparison of enterotoxigenic Escherichia coli isolated from humans and swine: insights into host specificity.
Breyer GM, Bernardes JS, Dorn M … +1 more , Siqueira FM
Mol Genet Genomics · 2026 Apr · PMID 42029767 · Full text
Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is a common threat to humans and animals. Clinical ETEC strains display host tropism, usually driven by adherence and toxin-host interactions in the gut. Other v...
Diarrhea caused by enterotoxigenic Escherichia coli (ETEC) is a common threat to humans and animals. Clinical ETEC strains display host tropism, usually driven by adherence and toxin-host interactions in the gut. Other virulence factors, metal acquisition mechanisms, and immune evasion strategies may also influence host specificity. Using publicly available genomes, we performed a pangenomic and functional comparison of 77 human- and swine-derived ETEC strains. Sequence types ST10 and ST4 found in both hosts, suggesting potential cross-host transmission. Phylogenetic analyses showed clustering mainly by ST, regardless of host or geography. Additionally, most functional domains were shared between hosts; however, human-derived strains carried exclusive domains related to adhesion, transposition, and toxins, whereas swine-derived strains harbored domains linked to stress response and metal binding. Notably, the PF09075 domain from the STb enterotoxin occurred only in swine-derived strains, despite previous reports in humans. Comparative analyses of STa (PF02048) and STb revealed no structural or functional homology but confirmed the swine-specific association of STb and greater sequence STa variability in human-derived strains. These findings indicate that sequence and functional differences in these enterotoxins contribute to ETEC host tropism, while ST patterns reveal possible epidemiological links between human and swine infections.
In silico characterization of melanoma-derived mouse lncRNA Gm26982 and comparative analyses with human ortholog.
Majumder S, Lodh E, De T … +1 more , Chowdhury T
Mol Genet Genomics · 2026 Apr · PMID 42029703 · Publisher ↗
Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cancer progression; however, the majority remain functionally uncharacterized, limiting their translational and clinical...
Long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and cancer progression; however, the majority remain functionally uncharacterized, limiting their translational and clinical relevance. In particular, the extent to which lncRNA functions are conserved across species and contribute to melanoma progression remains poorly understood. This study presents an integrative in silico characterization of mouse lncRNA Gm26982, previously implicated in melanoma models, alongside comparison with its human counterpart LINC00852, to elucidate structural, regulatory, and functional conservation with potential translational and clinical relevance. We implemented a comprehensive and robust bioinformatics pipeline integrating diverse computational tools, web servers, and publicly available databases to systematically evaluate the coding potential, synteny, sequence conservation, expression profiles, subcellular localization, secondary structure, and interaction networks of Gm26982, including its associations with miRNAs and RNA-binding proteins. Our results demonstrate that Gm26982 possesses low coding potential despite a complete reading frame, and is predominantly expressed in neural and immune-related murine tissues. Synteny analysis established its ortholog in human LINC00852 with overlapping expression domains and subcellular localization. Despite modest sequence similarity, both lncRNAs share conserved genomic contexts, overlapping tissue-specific expression patterns, and similar regulatory interactions. Notably, both transcripts were predicted to interact with miR-140-3p, suggesting a conserved regulatory mechanism potentially mediated through competing endogenous RNA (ceRNA) activity. Structural analysis further revealed differences in thermodynamic stability and folding complexity, indicating evolutionary divergence in regulatory capacity. Collectively, these findings suggest that Gm26982 and LINC00852 represent conserved lncRNAs with potential roles in melanoma-associated regulatory networks, particularly through miRNA-mediated post-transcriptional regulation. This study provides a foundation for future experimental validation. It highlights the importance of integrative computational approaches in identifying functionally relevant lncRNAs, with potential implications for biomarker discovery and therapeutic targeting in cancer.
SND1 regulates the androgen signaling axis by stabilizing EIF3B mRNA to facilitate the deterioration of prostate cancer.
Li Y, Yang C, Cui G … +5 more , Gui S, Jia L, Chen Y, Niu H, Xin H
Mol Genet Genomics · 2026 Apr · PMID 41986545 · Publisher ↗
Prostate cancer (PCa) progression relies heavily on activation of the androgen signaling pathway, mediated by the androgen receptor (AR). Emerging evidence has shown that SND1 contributes to drug resistance and tumor gro...
Prostate cancer (PCa) progression relies heavily on activation of the androgen signaling pathway, mediated by the androgen receptor (AR). Emerging evidence has shown that SND1 contributes to drug resistance and tumor growth of PCa. Therefore, this study aims to elucidate further the molecular mechanism by which SND1 promotes PCa progression through its post-transcriptional regulation of AR, intending to identify potential therapeutic targets for this disease. Our results revealed that SND1 and EIF3B were significantly elevated in PCa cells. Knockdown of either SND1 or EIF3B suppressed the PCa cell viability, proliferation, and migratory and invasive abilities of PCa cells. Mechanistically, SND1 directly bound to and enhanced the stability of EIF3B mRNA. Furthermore, EIF3B interacted with AR mRNA, thereby facilitating the translation process and AR protein levels. Notably, EIF3B overexpression counteracted the suppressive effects following SND1 knockdown on the aggressive characteristics of PCa cells. This study uncovers a novel SND1/EIF3B/AR regulatory axis in PCa, wherein SND1 stabilizes EIF3B mRNA, thereby enhancing AR translation and driving tumor progression. These findings highlight SND1 and EIF3B as promising prognostic biomarkers and potential therapeutic targets for advanced PCa.
pka1 deletion induces hyperactivation of the transcription factor Mca1 and drives chromosome mis-segregation in Schizosaccharomyces pombe.
Yamawaki M, Nishioka S, Matsuo Y
Mol Genet Genomics · 2026 Apr · PMID 41984257 · Full text
The cAMP-dependent protein kinase (PKA) pathway is required for proper chromosome segregation in Schizosaccharomyces pombe. Deletion of pka1 gene causes chromosome mis-segregation and sensitivity to microtubule-depolymer...
The cAMP-dependent protein kinase (PKA) pathway is required for proper chromosome segregation in Schizosaccharomyces pombe. Deletion of pka1 gene causes chromosome mis-segregation and sensitivity to microtubule-depolymerizing drugs. We have previously identified rst2∆, tfs1∆, mca1∆, and moc3∆ as suppressors of the pka1∆ phenotype, implicating transcriptional-related factors in the process. In the present study, we show that mca1 deletion suppresses both TBZ sensitivity and chromosome mis-segregation in pka1∆ cells. Mca1 contains an N-terminal DNA-binding domain that is required for suppression of TBZ sensitivity in the pka1∆ strain. Mca1 expression levels were higher in pka1∆ cells than in wild-type cells, and overexpression of Mca1 induced TBZ sensitivity and a high frequency of chromosome mis-segregation, indicating that appropriate Mca1 protein levels are critical for accurate chromosome segregation. The combined deletion of mca1, rst2, and tfs1 resulted in stronger suppression of TBZ-induced growth inhibition in pka1∆ cells compared with any single deletion, suggesting that these factors function in parallel or partially independent pathways rather than in a single linear pathway. Consistently, the high frequency of chromosome mis-segregation observed in pka1∆ cells was reduced by combinations of mca1∆, tfs1∆, and rst2∆, with tfs1∆ showing the strongest, mca1∆ moderate, and rst2∆ the weakest suppressive effects. Taken together, these findings demonstrate that transcriptional mis-regulation mediated by Mca1, Tfs1, and Rst2 contributes to defective chromosome segregation in the absence of functional Pka1.
Knockout of kdm4aa inhibits early embryonic development in zebrafish via downregulating cyp26a1.
Deng R, Cai X, Jiang H … +4 more , Luo Y, Chai W, Han B, Zhang J
Mol Genet Genomics · 2026 Apr · PMID 41984249 · Publisher ↗
Histone lysine demethylase 4A (KDM4A) plays crucial roles in regulating cell proliferation, differentiation, development and tumorigenesis, however its roles in fish are unclear. There are two copies of the kdm4a gene in...
Histone lysine demethylase 4A (KDM4A) plays crucial roles in regulating cell proliferation, differentiation, development and tumorigenesis, however its roles in fish are unclear. There are two copies of the kdm4a gene in zebrafish (Danio rerio), namely kdm4aa and kdm4ab. Our previous study showed that knockout of kdm4aa severely disturbs early embryonic development in zebrafish, here we investigated the underlying mechanism. Knockout of kdm4aa in zebrafish resulted in a clear developmental delay and embryonic lethality, accompanied by increased apoptosis. RT-qPCR and CUT&Tag-qPCR showed kdm4aa knockout downregulated Cytochrome P450 26a1 (cyp26a1), probably through elevated enrichment of H3K9me3 and reduced enrichment of H3K4me3 at promoter region of cyp26a1. Further experiments confirmed that cyp26a1 mRNA partially alleviates stress-induced apoptosis in both WT and kdm4aa knockout embryos, consistent with its known anti-apoptotic function. Our study helps understanding the key functions and mechanisms of kdm4aa in regulating early embryonic development in zebrafish.
Molecules of mood: the integrated molecular transducers of exercise's antidepressant effects.
Yuan D
Mol Genet Genomics · 2026 Apr · PMID 41964790 · Publisher ↗
Regular physical exercise exerts robust antidepressant effects, yet the molecular mechanisms underlying this phenomenon remain incompletely defined. Emerging evidence highlights exercise as a systemic stimulus that orche...
Regular physical exercise exerts robust antidepressant effects, yet the molecular mechanisms underlying this phenomenon remain incompletely defined. Emerging evidence highlights exercise as a systemic stimulus that orchestrates a network of peripheral and central molecular transducers, collectively modulating mood and resilience to stress. Key mediators include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), myokines like irisin, metabolic regulators including lactate and kynurenine pathway metabolites, and immune-derived cytokines that recalibrate neuroinflammation. These molecules converge on neural circuits of reward, motivation, and affect, promoting synaptic plasticity, neurogenesis, and homeostatic balance in monoaminergic signaling. Integrative frameworks suggest that exercise-induced molecular crosstalk between muscle, liver, adipose tissue, immune system, and brain constitutes a dynamic “molecular transducer network” that underpins its antidepressant efficacy. Understanding this interconnected biology not only advances mechanistic insight into exercise as medicine but also informs the development of novel therapeutic strategies that mimic or potentiate its mood-enhancing effects.
Phosphosite-centric regulatory network of ATAD2 and its involvement in transcriptional networks.
Fahma A, Lubaba F, Mohan A … +3 more , Sekhar PS, Gopalakrishnan AP, Raju R
Mol Genet Genomics · 2026 Apr · PMID 41964706 · Publisher ↗
The phosphorylation dependent regulation of transcription factors, transcriptional co-regulators and chromatin remodelling factors influences transcription. Aberrant transcriptional regulations driven by chromatin-associ...
The phosphorylation dependent regulation of transcription factors, transcriptional co-regulators and chromatin remodelling factors influences transcription. Aberrant transcriptional regulations driven by chromatin-associated oncogenic factors are a feature of various cancers; however, their phosphorylation-dependent regulation remains poorly characterised. ATPase family AAA domain-containing protein 2 (ATAD2) is a chromatin-associated factor implicated in oncogenic transcriptions. Here, we present a comprehensive phosphosite-centric analysis of ATAD2 by integrating data from multiple phosphoproteomic studies, encompassing 859 profiling and 285 differential datasets. From the class 1 differentially regulated phosphosites, four predominant phosphosites-S327, S337, S342, and T1152, emerged as consistently regulated and were frequently detected in diverse tumour datasets. The co-differentially phosphorylated proteins, including their interactors and potential upstream kinases (HASPIN, STK10, CDK12, PRP4K, CDK13, PAK4), were involved in cell cycle, chromatin remodelling, transcription, and DNA repair. Several phosphosites in transcription factors were found to be coregulated along with ATAD2 phosphosites. Phosphorylation at S327 and S342 was broadly upregulated and positively associated with transcriptional activators, suggesting a role in promoting transcription. In contrast, phosphorylation at S337 and T1152 correlated with proteins involved in transcriptional repression, indicating its involvement in inhibitory function. Collectively, these findings indicate the involvement of the ATAD2 phosphoregulatory network in transcriptional regulation and provide insights into the regulatory landscape of ATAD2, laying the groundwork for its potential therapeutic targeting in cancers.
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