Mol. Genet. Genomics [JOURNAL]
Sun
200 papers
Integrating HTS and CRISPR/Cas for next-generation nucleic and non-nucleic acid diagnostics.
Mishra MK, Pamu S, Guptha PM … +6 more , Vanangamudi M, Mittapalli SK, Dash PP, Thakor V, Yanadaiah P, Patyar S
Mol Genet Genomics · 2026 Jun · PMID 42297998 · Publisher ↗
The synergy between HTS and CRISPR/Cas is changing how genes, biomarkers, and diseases are studied. Very useful due to the ability to scan entire molecular libraries in a single assay and its extreme rapidity. CRISPR/Cas...
The synergy between HTS and CRISPR/Cas is changing how genes, biomarkers, and diseases are studied. Very useful due to the ability to scan entire molecular libraries in a single assay and its extreme rapidity. CRISPR/Cas systems, however, are crucial for achieving control and specificity, properties essential for precise genetic editing and targeted detection. HTS could be combined with CRISPR in two ways: HTS would expand the search space, and CRISPR would narrow it. This perspective highlights recent advances in which both platforms have been used together - for example, to find genetic variants and molecular markers in cancer, infectious diseases, and even biosensors to track the environment and metabolism. We discuss technical advances as well as practical issues that make the use of CRISPR/Cas more challenging in the clinical environment, including off-target activity, reproducibility, and the increasing complexity and dimensionality of data.
Nocardia fodinahabitans sp. nov. isolated from underground hard coal mine waters shows biotechnological potential for degradation of aromatic hydrocarbons.
Marciniak J, Sørensen T, Nowak A … +9 more , Noszczyńska M, Smoliński J, Machnik K, Solska K, Pala M, Hansen FT, Søndergaard T, Paściak M, Siupka P
Mol Genet Genomics · 2026 Jun · PMID 42297994 · Full text
The aim of the study was to describe and evaluate the biotechnological potential of a novel species of Nocardia isolated from underground coal mine water. Nocardia strains represent important human pathogens, but are als...
The aim of the study was to describe and evaluate the biotechnological potential of a novel species of Nocardia isolated from underground coal mine water. Nocardia strains represent important human pathogens, but are also common in soil and water environments. Recently, they have gained attention for their biosynthetic potential and vast metabolic abilities to degrade aromatic compounds, including xenobiotics. In this work, we established the taxonomic status of strain MW-W600-9. Phylogenetic analysis based on 16 S rRNA gene and whole genome sequencing revealed close relatedness to Nocardia rhizosphaerihabitans and Nocardia asteroides. This is further supported by phenotyping tests, chemotaxonomic analyses and MALDI-ToF profiling. We therefore propose that strain MW-W600-9 (= DSM 120649 =PCM 3565) constitutes a new species, Nocardia fodinahabitans sp. nov. The strain has 31 putative biosynthetic gene clusters, 12 showing low or no similarity to the clusters of known compounds, indicating its potential to produce novel bioactive compounds. The strain MW-W600-9 shows degradation potential of aromatic xenobiotics, tested for haloorganic compounds and bisphenols. The concentration of 4-chlorophenol and bisphenol A was decreasing significantly during the strain culture, and the results suggest co-metabolic removal of iohexol. This work shows the biodegradation ability of aromatic xenobiotic compounds by a new species of Nocardia, highlighting the potential use of the strain in bioremediation applications. It also shows for the first time the degradation of bisphenol by a member of the Nocardia genus, along with potential co-metabolic degradation of environmentally persistent haloorganic compounds.
Comparative genome analysis of carbapenemase-producing Pseudomonas aeruginosa: gene diversity, clonal distribution, and genome dynamics.
Noori Goodarzi N, Badmasti F
Mol Genet Genomics · 2026 Jun · PMID 42234203 · Publisher ↗
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) represents a major health threat due to its extensive resistance to last‑resort antibiotics. Although carbapenemase determinants are key drivers of global CRPA dissemina...
Carbapenem-resistant Pseudomonas aeruginosa (CRPA) represents a major health threat due to its extensive resistance to last‑resort antibiotics. Although carbapenemase determinants are key drivers of global CRPA dissemination, comprehensive genomic investigations delineating their chromosomal versus plasmid contexts are sparse. Therefore, in this study we conducted an integrated comparative genomic analysis of P. aeruginosa strains harboring major carbapenemase genes (bla, bla, bla, bla, bla, and bla), with a focus on their genomic localization, surrounding genetic architectures, and associated mobility elements. Chromosomes and plasmids carrying carbapenemase genes (retrieved from GenBank through 2025) were systematically characterized for sequence types, genetic environments, co‑occurring antimicrobial resistance genes (ARGs), and plasmid mobility features using established bioinformatic pipelines. Genetic relatedness of plasmids was inferred via ClustAGE and UPGMA clustering. Multilocus sequence typing (MLST) was employed to assess clonal relatedness of isolates. Among 398 carbapenemase-carrying genomic fragments, bla, bla, and bla were the most prevalent. bla, bla, and bla showed broad geographic distribution. High-risk clones including ST235, ST111, ST233, ST357, ST308, and ST277 were among the most common sequence types. Notably, a minority (10.28%) of carbapenemase-carrying plasmids were predicted to be conjugative or mobilizable. The mex, and opr families, and sul1 were most frequent co-existing ARGs. These findings highlight the dominant role of established high-risk lineages and integrative mobile elements in shaping the epidemiology of resistance. The relatively low frequency of self-transmissible plasmids suggests that horizontal resistance dissemination is likely mediated through a combination of integrative mobile genetic elements and clonal expansion. Our results underscore the necessity for enhanced genomic surveillance strategies that integrate clonal tracking with mobile resistance determinant monitoring to better understand and control the spread of carbapenem resistance.
RNA-binding protein hnRNPD induces epithelial-mesenchymal transition in Wilms' tumor via facilitating MAP4K4 mRNA stability.
Li G, Liao M, Bao H … +6 more , Xu H, Wang J, Zhang M, Li C, Zheng T, Yang C
Mol Genet Genomics · 2026 Jun · PMID 42234174 · Publisher ↗
Wilms' tumor (WT) is one of the most common pediatric abdominal malignancies. The RNA-binding protein heterogeneous nuclear ribonucleoprotein D (hnRNPD) is related to cancer progression through regulating target mRNA sta...
Wilms' tumor (WT) is one of the most common pediatric abdominal malignancies. The RNA-binding protein heterogeneous nuclear ribonucleoprotein D (hnRNPD) is related to cancer progression through regulating target mRNA stability. Nonetheless, its expression profile and value for WT are largely unexplored. Human renal proximal tubular epithelial cells (RPTEC) and WT cells (17.94, HFWT) were employed as experimental models for exploring hnRNPD's effect on WT progression. Subsequently, potential downstream targets of hnRNPD were identified through bioinformatics analysis. Functional validation was performed in vitro by modulating hnRNPD and its candidate targets via gene silencing and overexpression methods. Alterations in gene expression was analyzed through qRT-PCR as well as Western blot. Besides, CCK-8 was conducted to evaluate cell proliferation, whereas scratch and Transwell assays to determine cell migration alongside invasion separately. Additionally, critical epithelial-mesenchymal transition (EMT)-associated protein expression, namely E-cadherin, N-cadherin, alongside vimentin, was detected to assess regulatory impact of hnRNPD on the EMT process. hnRNPD mRNA and protein expression significantly elevated within 17.94 and HFWT cells than in RPTEC cells. Silencing of hnRNPD in 17.94 cells inhibited cell proliferation, migration, and invasion. Concurrently, N-cadherin and Vimentin protein levels declined, and E-cadherin protein level increased. Conversely, overexpression of hnRNPD in HFWT cells markedly enhanced their malignant phenotypes and promoted EMT. Bioinformatics analysis identified mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) as a potential downstream target of hnRNPD in WT. Mechanistically, hnRNPD overexpression extended the half-life of MAP4K4 mRNA, and a specific physical interaction between hnRNPD protein and MAP4K4 mRNA was observed. Functional rescue experiments further demonstrated that silencing MAP4K4 inhibited tumor malignant progression, while overexpression of MAP4K4 reversed the tumor-suppressive effects induced by hnRNPD silencing. hnRNPD may promote EMT in WT cells by stabilizing MAP4K4 mRNA, suggesting a critical role for the hnRNPD-MAP4K4 axis in driving tumor progression.
Therapeutic target exploration of Shugan Jianpi formula in liver fibrosis: an integrated lncRNA-mRNA co-expression network analysis.
Wan K, Zhou Q, Feng R … +5 more , Fan C, Shi W, Xu W, Jiang H, Zhou Q
Mol Genet Genomics · 2026 Jun · PMID 42233997 · Publisher ↗
Shugan Jianpi Formula (SGJPF), a traditional Chinese herbal formulation, has been clinically used for decades in the management of various chronic liver diseases, including liver fibrosis (LF). Previous studies have demo...
Shugan Jianpi Formula (SGJPF), a traditional Chinese herbal formulation, has been clinically used for decades in the management of various chronic liver diseases, including liver fibrosis (LF). Previous studies have demonstrated the efficacy of SGJPF in ameliorating pathological manifestations in murine models of LF. However, the precise molecular mechanisms underlying its therapeutic effects remains unclear. In the present study, we aimed to explore the therapeutic mechanisms of SGJPF through comprehensive analysis of LncRNA-mRNA co-expression network.The therapeutic efficacy of SGJPF in a CCL-induced LF murine model was assessed by histopathological alterations, α-smooth muscle actin (α-SMA) and collagen Ⅰ expression. To elucidate the molecular mechanisms underlying the efficacy of SGJPF, whole transcriptome RNA sequencing technology was conducted to identify the LncRNAs and mRNAs expression profiles across control, model, and SGJPF-treated groups. GO function and KEGG pathway enrichment analysis was performed to identify the biological functions and signaling pathways associated with the differentially expressed genes (DEGs). Subsequently, the hub LncRNAs and mRNAs were identified based on fold change and correlation analysis. Finally, biological relevance of these core genes were further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in mouse liver tissue, revealing the regulatory interactions between LncRNAs and their target mRNAs. Compared with the control group, 401 differentially expressed (DE) LncRNAs and 1224 DE mRNAs were found in the model group. In addition, compared with the model group, 98 DE LncRNAs and 147 DE mRNAs were identified following treatment with SGJPF. Subsequently, 31 DE LncRNAs and 39 DE mRNAs were obtained and served as potential target genes of SGJPF. Functional annotation of the 31 DE LncRNAs revealed predominant involvement in small molecule metabolic processes, with significant associations observed in circadian rhythm regulation, p53 signaling pathway, TGF beta signaling pathway, and Hippo signaling pathway. Correlation analysis indicated significant associations between these 31 DE LncRNAs and 39 DE mRNAs (|PCC|> 0.65, P < 0.05). Additionally, the expression of 2 LncRNAs (Gm28857, D030074P21Rik) and 5 mRNAs (Cdkn1a, Id1, Id4, Wnt9b, Gadd45g) were confirmed by RT-qPCR in mouse liver tissue, which were consistent with RNA sequencing data. This study delineates the comprehensive LncRNA/mRNA expression profiles in LF treated with SGJPF, which may provide valuable insights into the molecular mechanisms underlying LF pathogenesis and identifying potential therapeutic targets for further investigation.
Berberine impedes the DNA damage repair to inhibit colorectal cancer by regulating the SOX17/TCF4/PIM3 axis.
Hu F, Wang W, Li M … +3 more , Shi Q, Que J, Huang P
Mol Genet Genomics · 2026 May · PMID 42201413 · Publisher ↗
High levels of DNA damage repair (DDR) can promote the survival, immune evasion, and drug resistance of colorectal cancer (CRC) cells, consequently facilitating the advancement of CRC. This study was designed to investig...
High levels of DNA damage repair (DDR) can promote the survival, immune evasion, and drug resistance of colorectal cancer (CRC) cells, consequently facilitating the advancement of CRC. This study was designed to investigate the inhibitory effect of berberine (BBR) on CRC progression and the underlying mechanism involving DDR regulation, to provide a novel theoretical basis for clinical CRC treatment. First, we found that BBR demonstrated a dose-dependent inhibition of the viability of CRC cells. BBR promoted apoptosis and suppressed the DDR in CRC cells by upregulating SOX17. Overexpression of SOX17 restrained CRC cell viability and facilitated cell apoptosis. BBR inhibited the DDR of CRC cells by inactivating the β-catenin/TCF4 pathway through the regulation of SOX17. Furthermore, TCF4 transcriptionally activated PIM3 expression. Knockdown of SOX17 partially eliminated the suppressive effects of BBR on CRC cell viability and DDR. Conversely, PIM3 silencing reversed the effects of SOX17 knockdown. In conclusion, we demonstrated BBR inhibits DDR in CRC cells via mediating the SOX17/TCF4/PIM3 axis, thereby blocking CRC progression. This regulatory axis serves as a potential therapeutic target for CRC, and BBR holds promising application prospects as a DDR inhibitor in CRC clinical intervention.
The causality between physical activity and gestational diabetes mellitus: a Mendelian randomization study.
Ma X, Liu Y, Xu X … +2 more , Wang H, Zhao X
Mol Genet Genomics · 2026 May · PMID 42201408 · Publisher ↗
Although observational research shows that physical activity and sedentary behavior are associated with the risk of gestational diabetes mellitus (GDM), lipid, and body mass index (BMI), their causal direction and potent...
Although observational research shows that physical activity and sedentary behavior are associated with the risk of gestational diabetes mellitus (GDM), lipid, and body mass index (BMI), their causal direction and potential mediating mechanism are still unclear, which limits the development of precise prevention strategies. Based on the genetic data on the European ancestry population, the study aimed to investigate the causal relationship of GDM with physical activity and sedentary behavior using Mendelian randomization (MR), and quantify the mediating roles of BMI and lipids in it. The bidirectional dual sample MR analysis based on whole genome association research data revealed that there was a significant negative causal association between physical activity time and the risk of GDM in females (OR = 0.977, 95% CI: 0.956-0.998, P = 0.030), while leisure screen time had a positive causal association with the risk of developing GDM (OR = 1.125, 95% CI: 1.023-1.238, P = 0.015). Mediation analysis indicated that BMI was the primary causal pathway for reducing the risk of GDM through physical activity time, with a mediation ratio of 53.6%. Multivariate MR analysis showed that after adjusting for BMI, the direct effect was no longer significant, indicating that BMI played a major and almost complete mediating role. In the causal pathway of increased GDM risk in leisure screen time, BMI, high-density lipoprotein cholesterol (HDL-C), and Apolipoprotein A1 (ApoA1) effectively mediated the causal relationship between leisure screen time and GDM risk, with mediation proportions of 81.8%, 11.2% and 10.1%, respectively. Physical activity can indirectly reduce the risk of GDM by lowering BMI, while excessive leisure screen time significantly increases the risk of GDM by affecting BMI, HDL-C, and ApoA1. These findings support the potential value of prioritizing weight control and integrating interventions that increase physical activity and limit sedentary behavior as core measures, in order to fundamentally block the pathway of GDM by synergistically optimizing weight and lipid metabolism.
Targeting KIF18B overcomes oxaliplatin resistance in esophageal squamous cell carcinoma via suppression of the ATR/CHK1 axis.
Liu W, Wang Q, Tan X … +2 more , Cao C, Tian B
Mol Genet Genomics · 2026 May · PMID 42201394 · Publisher ↗
Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, frequently driven by chemotherapy resistance. Kinesin family member 18B (KIF18B) is implicated in tumor progression, but its role in ESCC chemo...
Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, frequently driven by chemotherapy resistance. Kinesin family member 18B (KIF18B) is implicated in tumor progression, but its role in ESCC chemoresistance remains unclear. To investigate KIF18B's clinical relevance and mechanistic contribution to oxaliplatin resistance in ESCC, KIF18B expression was analyzed in TCGA data, ESCC cell lines/tissues (qPCR, Western blot, IHC), and correlated with survival (Kaplan-Meier). Results showed that, KIF18B was significantly elevated in ESCC and correlated with shorter overall/progression-free survival. Knockdown reversed oxaliplatin resistance, reducing IC50 from 8.5 µM to 3 µM, restoring apoptosis, and inducing G2/M arrest. Silencing suppressed the ATR/CHK1 pathway (reduced p-ATR, p-CHK1, WEE1, CDC25A) and increased γH2AX foci. Co-IP confirmed KIF18B-ATR interaction, suggesting stabilization of DNA damage signaling. In vivo, KIF18B knockdown synergized with oxaliplatin, achieving > 80% tumor suppression and reduced Ki-67/p-ATR/p-CHK1 levels. In conclusion, KIF18B is a prognostic biomarker and therapeutic target in ESCC. Its inhibition overcomes oxaliplatin resistance by disrupting KIF18B-ATR interaction and ATR/CHK1-mediated DNA repair. Combining KIF18B targeting with chemotherapy or ATR inhibitors represents a promising strategy for refractory ESCC.
Genome-wide identification, in-silico characterization, and expression analysis of polygalacturonases in different fungal species.
Amin L, Zafar I, Jamal A … +3 more , Safeer Mehdi Bokhari SM, Bahwerth FS, Noman M
Mol Genet Genomics · 2026 May · PMID 42191998 · Publisher ↗
Polygalacturonases (PGs) are key enzymes that hydrolyze pectin, a complex polysaccharide in plant cell walls, with essential roles in biological processes and industrial applications. This study presents a comprehensive...
Polygalacturonases (PGs) are key enzymes that hydrolyze pectin, a complex polysaccharide in plant cell walls, with essential roles in biological processes and industrial applications. This study presents a comprehensive genome-wide identification and in-silico characterization of PGs from four fungal species: Aspergillus oryzae, Aspergillus flavus, Neurospora crassa, and Rhizoctonia solani. A total of 44 PG protein sequences were retrieved from the NCBI database, confirming the presence of the Glyco_hydro_28 (GH28) domain, which is essential for pectin hydrolysis. Phylogenetic analysis using the Neighbor-Joining method revealed four major clades (A, B, C, D), with A. flavus and A. oryzae sharing a close evolutionary relationship (bootstrap support = 93%). Gene structure analysis revealed that A. flavus (Af1) and A. oryzae (Ao1) each have one exon, while Neurospora crassa (NSc1) contains one intron. Ten conserved motifs were identified, with Motif 1 present in Rz1, Rz2, and Rz5, and Motif 2 in all sequences except Ao15 and Ao16. Chromosomal mapping indicated species-specific gene distributions, with A. oryzae showing genes spread across five chromosomes. Gene expression analysis of A. oryzae under various growth conditions revealed 20 differentially expressed genes (DEGs), including 10 upregulated (e.g., Gene_Ao1, LFC = 2.50, FDR = 0.00450) and 10 downregulated (e.g., Gene_AO9, LFC = -2.87, FDR = 1.1e-05). Pathway enrichment analysis highlighted significant involvement of PGs in apoptosis (FDR = 1.2e0), cell cycle regulation (FDR = 9.7e), and DNA repair (FDR = 2.3e). Protein-protein interaction (PPI) network analysis revealed 41 nodes and 400 edges, with an average node degree of 19.5. Structural modeling of the expressed protein LOCUS (XP_Ao1820953) with PDB ID: 5ZU2 showed high stability and flexibility, supported by molecular dynamics simulations. These results provide new insights into the evolutionary, structural, and functional roles of fungal PGs, with implications for their applications in biofuel production, food processing, and fiber retting.
UCMSC-derived exosomal circDLGAP4 enhances HFF-1 cell proliferation and migration by promoting ZNF217 promoter H3K27 acetylation.
Ma YL, Fu J, Zhang YX … +6 more , Xue HY, Luo YY, Zhang WZ, Kuang SJ, Xu JQ, Liang ZH
Mol Genet Genomics · 2026 May · PMID 42191952 · Publisher ↗
Umbilical cord mesenchymal stem cells (UCMSCs) have been shown to actively participate in diabetic foot ulcer (DFU) wound healing. The human foreskin fibroblast-1 (HFF-1) cell line is a crucial and widely used in vitro m...
Umbilical cord mesenchymal stem cells (UCMSCs) have been shown to actively participate in diabetic foot ulcer (DFU) wound healing. The human foreskin fibroblast-1 (HFF-1) cell line is a crucial and widely used in vitro model for fundamental research on DFUs. In this study, the role of UCMSC-derived exosomal circDLGAP4 in high-glucose (HG)-stressed HFF-1 cells was clarified, in particular whether it regulates the TATA-box binding protein-associated factor 15 (TAF15)/p300/zinc finger protein 217 (ZNF217) axis to enhance cell proliferation and migration. We confirmed that UCMSC-derived exosomes that contained circDLGAP4 in abundance enhanced the proliferation and migration of HG-stressed HFF-1 cells. Under an HG environment, ZNF217 was downregulated in the HFF-1 cells, whereas its overexpression promoted the proliferation and migration of the cells, an effect facilitated by its own activation via the p300-mediated H3K27 acetylation of its gene promoter. The p300 mRNA was stabilized through interaction with TAF15, while the expression of TAF15 was upregulated through its interaction with circDLGAP4. Additionally, exosomal circDLGAP4 promoted wound healing in mice with DFUs. In conclusion, UCMSC-derived exosomal circDLGAP4 enhanced HFF-1 cell proliferation and migration under HG conditions in vitro and promoted diabetic wound healing in vivo by activating the TAF15/p300/ZNF217 axis.
FAM72A is associated with lung cancer proliferation and migration via the NF‑κB signaling pathway.
Gu Q, Shen Q, Liu T … +2 more , Jin L, Min W
Mol Genet Genomics · 2026 May · PMID 42174281 · Publisher ↗
Lung cancer remains the leading cause of cancer-related deaths worldwide. While the Family with sequence similarity 72 member A (FAM72A) gene has been implicated in various cancers, its role in lung cancer is yet to be d...
Lung cancer remains the leading cause of cancer-related deaths worldwide. While the Family with sequence similarity 72 member A (FAM72A) gene has been implicated in various cancers, its role in lung cancer is yet to be determined. This study aimed to investigate the role of FAM72A in lung cancer and the underlying mechanism. Bioinformatic analysis of The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) dataset revealed that FAM72A was significantly upregulated in lung adenocarcinoma tissues, and high FAM72A expression was closely associated with poor patient prognosis. Western blot analysis revealed that FAM72A protein expression was significantly upregulated in multiple lung cancer cell lines (A549, H1299, and H460) compared to normal lung epithelial cells. Through a series of assays including flow cytometry, MTT, clone formation, wound healing, and Transwell experiments, we demonstrated that knockdown of FAM72A via shRNA effectively suppressed proliferation and migration in A549 and H1299 cells, while promoting apoptosis. Additionally, in vivo studies using a mouse xenograft model confirmed that FAM72A knockdown inhibited tumor growth. Mechanistic analyses showed that FAM72A knockdown is associated with inactivation of the NF‑κB signaling pathway, as knockdown led to decreased expression of p-IkBα, p-IKKα, p-NF-κB, Cyclin D1, and PCNA. In conclusion, our findings demonstrate that FAM72A contributes to lung cancer progression by regulating the activity of the NF‑κB signaling pathway, suggesting its potential as a therapeutic target for lung cancer.
Integrated transcriptomic and metabolomic investigation reveals that graphene oxide reduces nicosulfuron detriment in sweet corn.
Wang Y, Zhong X, Zhang M … +1 more , Wang J
Mol Genet Genomics · 2026 May · PMID 42159781 · Publisher ↗
Nicosulfuron (NIF) stress poses a significant constraint on sweet corn production. Graphene oxide (GO), as an environmentally friendly nanomaterial, serves as a safe agent to enhance crop stress resistance. However, the...
Nicosulfuron (NIF) stress poses a significant constraint on sweet corn production. Graphene oxide (GO), as an environmentally friendly nanomaterial, serves as a safe agent to enhance crop stress resistance. However, the molecular mechanisms of GO-mediated sweet corn to tolerate NIF remain largely unexplored. This study aimed to investigate the regulatory effects of GO on sweet corn's response to NIF through physiological assessments, comparative transcriptomic analysis, and metabolomic profiling. The findings indicate that the application of GO mitigates the detrimental effects of NIF stress on sweet corn seedlings, as evidenced by enhanced growth metrics, improved chlorophyll fluorescence parameters, and photosynthetic indicators. GO predominantly influences genes and metabolites related to the synthesis of flavonoids, phenylpropanoids, and calcium (Ca) signaling pathways to counteract NIF stress in sweet corn. Additionally, key genes associated with peroxidases (POD) and cytochrome P450 monooxygenases (CYP) were identified through the analysis of weighted gene co-expression networks (WGCNA). These genes play crucial roles in the response to NIF stress orchestrated by graphene oxide. In summary, this study demonstrates the synergistic regulatory effect of GO on NIF tolerance in sweet corn, providing valuable insights for developing NIF-resistant sweet corn varieties.
Genome comparison of the bacteria in Mycobacterium avium complex (MAC) reveals the role of translational selection in shaping codon usage patterns.
Banerjee A, Sur S
Mol Genet Genomics · 2026 May · PMID 42159624 · Publisher ↗
The Mycobacterium avium complex (MAC) houses several pathogens that cause diseases in humans, ruminants, and birds. They are widely distributed in soils and water worldwide. In immunocompromised humans, MAC is responsibl...
The Mycobacterium avium complex (MAC) houses several pathogens that cause diseases in humans, ruminants, and birds. They are widely distributed in soils and water worldwide. In immunocompromised humans, MAC is responsible for nodular bronchiectasis and fibrocavitary lung diseases. The treatment of lung diseases induced by MAC remains difficult owing to antibiotic intolerance and disease recurrence. In this study, we compared the genome sequences of 90 complete MAC genomes and explored the factors shaping codon usage bias in the bacteria within MAC. Additionally, we studied the relationship between codon bias and pathogenic adaptation. The genome sizes ranged from 4.7 to 6.5 Mb. Variation in the mobile genetic elements and the number of CRISPR candidates was observed amongst the bacteria within MAC. Synonymous codon usage analysis divulged variations among subspecies, high codon usage bias, substantial heterogeneity in codon usage patterns, and moderate use of optimal codons. High GC3 content and elevated levels of CAI (a metric for gene expression levels) in all probability assisted the bacteria within MAC in adjusting to different host environments. Translational selection pressure prevailed over compositional bias and mutational selection in these organisms. Our analysis revealed differences in the tRNA content amongst the bacteria in MAC. The translational selective pressure enabled the adaptation of these pathogenic bacteria to competitive pressure in diverse environments and niches by maintaining a lesser number of tRNAs and lower tAI values.
Ecotype-specific sensitivity to DNA methylation inhibitors in Arabidopsis cmt3 mutants.
Sun X, Du G, Kato A … +1 more , Ito H
Mol Genet Genomics · 2026 May · PMID 42159606 · Publisher ↗
DNA methylation inhibitors such as 5-aza-2'-deoxycytidine (5-Aza-2dC) are widely used to probe epigenetic regulation, yet genetic factors underlying natural variation in inhibitor sensitivity remain poorly understood. He...
DNA methylation inhibitors such as 5-aza-2'-deoxycytidine (5-Aza-2dC) are widely used to probe epigenetic regulation, yet genetic factors underlying natural variation in inhibitor sensitivity remain poorly understood. Here, we investigated ecotype-specific responses to 5-Aza-2dC in Arabidopsis thaliana, focusing on cmt3 mutants in the Columbia (Col-0) and Landsberg erecta (Ler) backgrounds. We found that cmt3 mutants displayed contrasting phenotypes depending on genetic background: Col-0 cmt3 mutants showed relative resistance to 5-Aza-2dC, whereas Ler cmt3 mutants exhibited pronounced sensitivity. Genetic analyses indicated that this enhanced sensitivity in the Ler background is recessive and cannot be explained solely by loss of CMT3 function. Through genetic mapping, we identified At1g34770 (NSE3) as a strong candidate modifier associated with 5-Aza-2dC sensitivity. A non-synonymous substitution in NSE3 correlated with growth inhibition under inhibitor treatment, and transgenic analyses further supported a contributory role for this gene. Together, our results demonstrate that natural genetic modifiers, including allelic variation in NSE3, shape ecotype-dependent responses to DNA methylation inhibition, highlighting the importance of genetic background in modulating epigenetic perturbations in plants.
KIRREL1 is a novel prognostic biomarker that promotes malignancy in gastric cancer via activation of the epithelial-mesenchymal transition pathway.
Lv H, Liu J, Jiang L … +2 more , Nie Z, Wang Y
Mol Genet Genomics · 2026 May · PMID 42154344 · Publisher ↗
Gastric cancer (GC) is a leading cause of cancer-related mortality characterized by aggressive metastasis and limited therapeutic options. Kin of IRRE-like protein 1 (KIRREL1) is an emerging cell surface protein whose sp...
Gastric cancer (GC) is a leading cause of cancer-related mortality characterized by aggressive metastasis and limited therapeutic options. Kin of IRRE-like protein 1 (KIRREL1) is an emerging cell surface protein whose specific oncogenic role in GC remains largely unknown. Therefore, the intention of this study was to comprehensively investigate the clinical relevance, biological functions, and underlying molecular mechanisms of KIRREL1 in GC progression. The expression and prognostic value of KIRREL1 were evaluated using data from The Cancer Genome Atlas (TCGA) and in vitro experiments. Gain- and loss-of-function studies were performed in GC cell lines to assess the effects of KIRREL1 on proliferation, 5-FU chemosensitivity, migration, and invasion. Western blotting was used to examine the regulation of epithelial-mesenchymal transition (EMT) markers. KIRREL1 was significantly upregulated in GC tissues and cell lines, and its high expression was strongly correlated with poor progression-free, disease-specific, and overall survival in patients. Functionally, KIRREL1 overexpression promoted GC cell proliferation, migration, and invasion, whereas its knockdown had the opposite effects. Furthermore, KIRREL1 knockdown sensitized GC cells to 5-FU treatment. Mechanistically, KIRREL1 was found to positively regulate the expression of the key EMT markers Vimentin, MMP2, and MMP9. Our findings identify KIRREL1 as a novel oncogene that actively promotes GC proliferation, 5-FU chemoresistance, and metastasis via the EMT pathway. Importantly, this establishes KIRREL1 as both a robust prognostic biomarker and a targetable driver of malignancy. Future clinical perspectives should explore the development of specific KIRREL1 inhibitors to overcome chemoresistance and suppress metastatic dissemination.
ProSSF: integrating sequence, structure, and gene ontology for prediction of protein stability, interaction, and function.
Jiang T, Zhu Y, Liu Z … +3 more , Yi X, Zhang Q, Song S
Mol Genet Genomics · 2026 May · PMID 42154341 · Publisher ↗
Protein sequences encode rich structural and functional information that governs how organisms respond to genetic variation, environmental challenge, and disease. However, existing computational methods typically rely on...
Protein sequences encode rich structural and functional information that governs how organisms respond to genetic variation, environmental challenge, and disease. However, existing computational methods typically rely on a single information source, whether sequence, structure, or functional annotation, and their predictive power is substantially reduced for low-homology proteins or orphan proteins. Here we present ProSSF (Protein Sequence-Structure-Function), a unified multimodal pretraining framework that performs masked pretraining on large-scale protein sequences, encodes three-dimensional structural information via a Geometric Vector Perceptron Graph Neural Network (GVP-GNN), integrates Gene Ontology (GO) semantics through a dual-path hierarchical encoder, and aligns all three modalities into a shared representation space via cross-modal attention. Evaluated across three downstream tasks, ProSSF achieves a Spearman correlation of 0.74 ± 0.009 on the TAPE protein stability benchmark, a mean Micro-F1 of 84.60% ± 0.9% on the SHS148K protein-protein interaction dataset under the stringent DFS partition, and comparable or superior Fmax and AUPR relative to state-of-the-art baselines across all three GO sub-ontologies. Ablation analyses demonstrate that structural geometry and GO functional semantics contribute complementary and task-dependent information, with the largest performance gains observed under low-homology conditions. Attention-based interpretability analyses further reveal that the model preferentially attends to biologically meaningful regions, such as kinase catalytic domains, without explicit supervision. This study provides a unified multimodal pretraining framework and demonstrates that jointly encoding sequence, structure, and functional semantics substantially improves the generalizability of protein property prediction. Future studies should validate this framework on larger, taxonomically diverse protein datasets and explore its potential applications in the functional annotation of disease-associated proteins and the identification of novel drug targets.
Mitochondrial genomes from RNA-Seq reveal phylogeny and selection in Mepraia (Hemiptera: Reduviidae).
de Siqueira E Silva MC, Guadanucci JPL, Belintani T
Mol Genet Genomics · 2026 May · PMID 42154327 · Full text
Despite the epidemiological importance of triatomine bugs as vectors of Trypanosoma cruzi, mitogenomic resources remain limited for many lineages, restricting evolutionary and comparative analyses. The endemic Chilean ge...
Despite the epidemiological importance of triatomine bugs as vectors of Trypanosoma cruzi, mitogenomic resources remain limited for many lineages, restricting evolutionary and comparative analyses. The endemic Chilean genus Mepraia is a notable example, with scarce mitochondrial genomic information despite its relevance to Chagas disease ecology and vector evolution. Here, we reconstructed partial mitochondrial genomes, including all 13 protein-coding genes, from RNA-Seq data for three Mepraia species. Phylogenetic analyses confirmed the monophyly of Mepraia and resolved interspecific relationships, whereas comparative analyses revealed heterogeneous patterns of intraspecific diversity, with elevated variation in M. parapatrica. Codon-based tests detected pervasive purifying selection together with localized signals of positive selection in oxidative phosphorylation genes, particularly NAD5, NAD6, NAD1, and COIII. These results show that transcriptomic data provide a reliable source for mitochondrial genome reconstruction in non-model insects and that adaptive signals can coexist with strong functional constraint in triatomine mitogenomes. Overall, this study expands mitogenomic resources for Triatominae, improves evolutionary inference in Mepraia, and provides a foundation for future integrative studies on diversification, mitochondrial evolution, and vector biology.
Functional characterization and allele-specific RNA interference-based rescue of KCNH2 p.F68C variant associated with long QT syndrome.
Zhao M, Han M, Li W … +8 more , Wang Z, Chen L, Zeng H, Zhou Z, Hu D, Cheng Y, Wang Q, Ke T
Mol Genet Genomics · 2026 May · PMID 42154296 · Publisher ↗
Long QT syndrome (LQTS) is an inherited life-threatening cardiac disorder characterized by delayed ventricular repolarization and increased risk of malignant arrhythmias. Among its subtypes, long QT syndrome type 2 (LQT2...
Long QT syndrome (LQTS) is an inherited life-threatening cardiac disorder characterized by delayed ventricular repolarization and increased risk of malignant arrhythmias. Among its subtypes, long QT syndrome type 2 (LQT2) is primarily caused by pathogenic variants in KCNH2, which encodes the human ether-à-go-go-related gene (hERG) potassium channel responsible for the rapid delayed rectifier current (I). However, the substantial functional heterogeneity among KCNH2 variants poses a major challenge for clinical interpretation and precision intervention. In this study, we sought to functionally characterize KCNH2 p.F68C variant (c.203T > G) identified in a Chinese LQT2 patient and to evaluate the feasibility of RNA interference-based modulation of its functional impact on the hERG channel. Using biochemical and electrophysiological analyses in HEK293T cells, we show that variant p.F68C causes a severe trafficking defect and exerts a dominant-negative effect on wild-type hERG channels, leading to markedly reduced rapid delayed rectifier potassium current (I). In contrast to several previously reported Per-Arnt-Sim (PAS) domain variants, the trafficking defect of p.F68C was resistant to reduced culture temperature, chemical chaperones, and pharmacological chaperones. Notably, allele-specific RNA interference selectively suppressed mutant hERG expression, alleviated dominant-negative interference, and partially restored hERG current density without detectable cytotoxicity. Together, these findings establish p.F68C as a loss-of-function KCNH2 variant and highlight allele-specific RNA interference as a variant-directed strategy that may serve as an alternative to suppression-replacement approaches, providing a basis for functional interpretation and precision therapeutic exploration of individual KCNH2 variants.
Microenvironmental pH and host-pathogen co-evolution potentially influence the structural architecture of junctional adhesion molecules.
Karagöl T, Karagöl A
Mol Genet Genomics · 2026 May · PMID 42154072 · Publisher ↗
Understanding how proteins dynamically adapt to diverse and changing physiological microenvironments is a fundamental challenge in modern biological sciences. Junctional adhesion molecules (JAMs) are a family of conserve...
Understanding how proteins dynamically adapt to diverse and changing physiological microenvironments is a fundamental challenge in modern biological sciences. Junctional adhesion molecules (JAMs) are a family of conserved proteins critically involved in immune regulation and cell adhesion. In this study, we investigate the evolutionary and structural dynamics of three paralogs across 274 mammalian taxa, which share similar tertiary structures but differ in isoelectric points (pI). By integrating phylogenetic modeling, partial correlation, network topology, and evolutionary molecular dynamics in physiological pH (6.5-10.5) gradient, we explored potential explanations driving this diversification. Our analysis identified JAM-B as a likely central node in the conservation network, with Lys and Cys residues as central evolutionary residues. Evolutionary mapping revealed recent episodic selection bursts across 17% to 26% of mammalian lineages, could indicate that specific functional interfaces are undergoing rapid, lineage-specific innovation. Notably, we identified episodic hotspots in JAM-A at the distal D1 viral entry interface, consistent with an ongoing host-pathogen arms race, and parallel adaptive clusters at the C-terminal motifs across all paralogs. AlphaMissense profiling revealed that acidic-> basic mutations exhibit significantly lower pathogenicity scores. In preliminary early-onset dynamics simulations, root-mean-square-deviation profiles could suggest a pI-stability relationship, JAM-A and JAM-C displayed biphasic pH-dependent deviations (at pH 8.0 and pH 8.5). Dynamics-aware evolutionary profiling identified key dynamic-conserved residues: JAM-A at Gln66, JAM-B at Gln36 and Val57, and JAM-C at several basic residues. Together, these results suggest that isoelectric divergence correlates with residue evolution and microenvironment-specific structural dynamics. Ultimately, our integrated computational framework provides genomic insights into paralog diversification, offering a testable architectural blueprint for targeted mutagenesis or therapeutic modulation of pH-sensitive adhesion processes.
Identification of oxidative stress-related hub genes and immune infiltration characterization in chronic spontaneous urticaria.
Li J, Gan H, Zhong Y … +1 more , Liu H
Mol Genet Genomics · 2026 May · PMID 42138757 · Publisher ↗
Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that substantially impairs patients' quality of life, yet its underlying pathogenesis remains incompletely understood. Oxidative stress (OS) has been p...
Chronic spontaneous urticaria (CSU) is an inflammatory skin disorder that substantially impairs patients' quality of life, yet its underlying pathogenesis remains incompletely understood. Oxidative stress (OS) has been proposed as a key contributing factor; however, the molecular mechanisms involved and their link to immune dysregulation are still unclear. This study aimed to systematically identify OS-related hub genes in CSU, investigate their association with immune infiltration, and evaluate their diagnostic potential. Expression profiles for urticaria were retrieved from the Gene Expression Omnibus (GEO) database. WGCNA identified OS-related module genes. Differential analysis, GSEA, PPI network, and ROC curve were used to screen OS-related hub genes, with their associations with immune infiltration and potential drug targets analyzed. Additionally, clinical blood samples from patients with CSU were collected to validate the expression levels of the hub genes via quantitative real-time PCR (qRT-PCR). Ten OS-related hub genes (e.g., HMGB1, PSMD1) were screened, with ROC AUC values > 0.76, indicating high diagnostic validity. Immune infiltration analysis revealed pronounced infiltration of 22 immune cell types in CSU patients, while hub gene HMGB1 showed significant negative correlations with activated dendritic cells and γδ T-cell abundance. 33 potential drugs targeting OS-related hub genes were predicted using DGIdb database. The qRT-PCR verification showed that the expression trends of the 9 candidate genes (HIST1H4H, HIST1H4D, SMARCC2, HMGB1, DDB2, TCF7L2, ITGA8, IRF4, and HSPA4) in the clinical samples were consistent with the results of the bioinformatics analysis, all exhibiting high diagnostic value (AUC > 0.76, p < 0.05). In this study, ten OS-related hub genes were identified, nine of which were validated for their diagnostic value in clinical samples. Several potential drug targets were also predicted. These findings provide new insights into the molecular classification, early diagnosis, and targeted therapy of CSU. Future studies involving larger clinical cohorts are warranted to validate these targets and further elucidate their roles in OS-driven CSU pathogenesis, thereby facilitating clinical translation.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe