Biochemical Genetics最新文献

Breast cancer is a prevalent and highly heterogeneous malignancy that continues to be a major global health concern. Voltage-gated sodium channels are primarily known for their role in neuronal excitability, but emerging evidence suggests their involvement in the pathogenesis of various cancers, including breast cancer. However, the effect of β-subunits on breast cancer cells is not yet studied. SCN3B, as a modulatory subunit, is of particular interest due to its less understood role in cancer biology. This research comprehensively investigates the clinical associations, diagnostic potential, and functional role of SCN3B in breast cancer, shedding light on its diverse implications from patient outcomes to molecular mechanisms. Our methods included clinical data analysis from The Cancer Genome Atlas (TCGA) breast cancer dataset, diagnostic analysis through ROC curves, differential gene expression analysis, SCN3B expression assessment in cell lines, overexpression experiments, and functional assays. Additionally, we constructed a protein-protein interaction network to explore potential mechanisms underlying SCN3B's impact. The study revealed significant clinical associations between SCN3B expression and various parameters such as tumor stage, race, age, histological type, molecular subtype, and hormone receptor status. SCN3B demonstrated strong diagnostic potential with an AUC of 0.95. It influenced the expression of over 800 genes, primarily associated with cell migration and extracellular matrix interactions. SCN3B exhibited distinct expression patterns between normal and breast cancer cell lines and successfully overexpressed in various breast cancer cell lines. This overexpression inhibited cell migration and invasion. Our research emphasizes SCN3B's clinical relevance, diagnostic potential, and influence on cell behavior in breast cancer, offering insights into its multifaceted role and therapeutic implications.

Anoctamin 6 (ANO6) has been implicated in the oncogenicity of malignancies. However, pan-cancer analysis of ANO6 to fully explore its role in tumors has not been performed and little is reported on its role in melanoma. The ANO6 expression levels, clinical correlation, prognostic significance, mutational profiles, immune infiltration pattern, immune checkpoints, immunomodulatory genes, tumor heterogeneity, and molecular function were explored via systematic bioinformatics analysis and multiple public databases. Subsequently, the biological functions of ANO6 in the pulmonary metastasis of B16F10 melanoma cells in vivo were assessed by experimental validation. Our findings have demonstrated that ANO6 was highly expressed in most cancers and associated with poorer prognosis in cancer patients. A close relationship was observed between ANO6 expression level and clinicopathological characteristics, tumor immunity, and tumor heterogeneity. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that ANO6 was associated with immune response and regulated many cancer-related pathways. Furthermore, a melanoma pulmonary metastasis mice model showed that ANO6 was overexpressed in lung metastasis tissues compared with corresponding normal tissues. Collectively, ANO6 may serve as reliable biomarkers to predict the prognosis for diverse types of cancer and as a prospective marker for melanoma progression.

In recent years, the BTB (Bric-a-brac/Tramtrack/Broad complex) gene family in plants has garnered widespread attention for its regulatory roles in plant growth and development. However, knowledge regarding BTBs in poplar trees remains limited. Here, we identified 94 BTB gene family members across the genome of Populus alba L. Through phylogenetic analysis, these members were classified into seven subfamilies and 16 branches, followed by comprehensive bioinformatics and biological analyses. Structural analysis revealed that poplar BTB gene family exhibits both high conservation and diversity, with distinct gene structures and protein features. Expression pattern analysis demonstrated differential expression of poplar BTB genes across various tissues, hormone treatments, and under drought stress, suggesting their potential roles in poplar growth and development and drought response. This study provides a vital foundation and reference for unraveling the BTB-involved regulatory mechanisms underlying poplar growth and development and drought response.

COVID-19, caused by SARS-CoV-2 infection, frequently induces thrombotic complications in affected individuals. P-selectin, a pivotal platelet marker, plays a central role in platelet-leukocyte aggregation, contributing to hemostasis and thrombosis. Additionally, D-dimer serves as an indicator of coagulation system activity, while miR-17-5p exhibits antiviral properties in respiratory infections. This study aimed to evaluate and compare the expression levels of D-dimer, P-selectin, and miR-17-5p in COVID-19 patients hospitalized in intensive care units (ICUs) and those in non-ICU wards. This cross-sectional study included 50 COVID-19 patients, divided into ICU and non-ICU groups. P-selectin expression was assessed using Flow cytometry, D-dimer levels were measured via chemiluminescence, and miR-17-5p expression was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Our analysis revealed no significant difference in P-selectin expression levels between ICU and non-ICU patients (p = 0.1068). However, the expression levels of D-dimer and miR-17-5p were significantly elevated in ICU patients compared to non-ICU patients, with corresponding p-values of 0.032 and 0.0176, respectively. The heightened expression of D-dimer and miR-17-5p in ICU patients suggests their potential utility as predictive biomarkers for assessing the hemostatic status of COVID-19 patients.

Genetic variations in the lipoprotein lipase (LPL) gene including the HindIII polymorphism (rs320) have been reported to modify fat metabolism, adiposity, and body weight. However, little attention has been given to the African population. The present study aimed to investigate the relationship between the rs320 gene polymorphism and a number of metabolic and anthropometric parameters in a sample of the Nigerian population. We recruited 236 participants for the study. The participants were required to sign informed consent forms after which information related to their calorie intake and utilization as well as anthropometric measurements were recorded. Plasma metabolic parameters were subsequently determined using an autoanalyzer. Genotyping for HindIII polymorphism was performed using the PCR-RFLP method. The frequencies (n) of T and G alleles were 0.841 (397) and 0.158 (75), while the frequencies (n) of TT, TG, and GG were 0.691(163), 0.301(71), and 0.01(2), respectively. The population was not in Hardy-Weinberg equilibrium (χ² = 3.717, df = 1, p = 0.841). The anthropometric parameters, the fasting blood glucose, and low-density lipoprotein cholesterol showed no association with the alleles, while plasma high-density lipoprotein cholesterol and total cholesterol were significantly higher among the G allele carriers. However, triglyceride and total protein were significantly higher among the non-G allele carriers. The LPL HindIII gene polymorphism is associated with changes in plasma lipid profile in a sample of the Nigerian population.

Sepsis, a life-threatening condition characterized by a systemic inflammatory response, leads to organ dysfunction and high mortality rates. Honeysuckle, a traditional herbal remedy, has shown promise in attenuating organ damage and inhibiting pro-inflammatory factors in sepsis. However, the underlying molecular mechanisms remain unclear. We employed a multi-omics approach to elucidate honeysuckle's potential therapeutic effects in sepsis. RNA sequencing was performed on blood samples from 22 sepsis patients and 10 healthy controls to identify differentially expressed genes. Network pharmacology was utilized to predict effective ingredients and therapeutic targets of honeysuckle in sepsis. Meta-analysis compared gene expression between sepsis survivors and non-survivors. Single-cell RNA sequencing was employed to localize target gene expression at the cellular level. We identified 1328 differentially expressed genes in sepsis, with 221 upregulated and 1107 downregulated. Network analysis revealed 15 genes linked to 12 honeysuckle components. Four genes-DPP4, CD40LG, BCL2, and TP53-emerged as core therapeutic targets, showing decreased expression in non-survivors but upregulation in survivors. Single-cell analysis demonstrated that these genes were primarily expressed in T cells and other immune cells, suggesting their role in regulating immune response and inflammation. This study uses single-cell RNA sequencing and network analysis to identify DPP4, CD40LG, BCL2, and TP53 as key regulatory targets in sepsis, providing insights into disease mechanisms and potential therapeutic interventions. Network pharmacology analysis suggests possible interactions with honeysuckle compounds, though experimental validation is needed.

Atherosclerosis is the main cause of coronary artery disease (CAD), and it is not easy to be detected at the early stage. To mine biomarkers for early diagnosis of CAD. Potential molecular mechanism was mined using the biological databases. The qPCR and western blotting were used to detect the expression of LINC01220, hsa-miR- 6727 - 5p, and FBLN5. Dual-luciferase report assay and overexpression experiment were used to explore the regulation among LINC01220, hsa-miR- 6727 - 5p, and FBLN5. The cell viability, migration, apoptosis, and senescence were evaluated by CCK- 8, transwell, Annexin V/PI staining, and detection of aging markers. The differentiation of human bone marrow monocytes (HBMMs) was evaluated by detecting the expression of CD68, CD86, and iNOS. The clinical analysis was performed based on the blood samples from healthy individuals and asymptomatic CAD patients. The receiver operating characteristic (ROC) curve and logistic regression analysis were used to evaluate the diagnostic value of LINC01220/hsa-miR- 6727 - 5p/FBLN5 in CAD. Overexpression of LINC01220 promoted FBLN5 expression by down-regulating hsa-miR- 6727 - 5p. LINC01220 rescued human aortic endothelial cell (HAEC) viability injury, apoptosis, and senescence induced by oxidized low-density lipoprotein (ox-LDL), and inhibited HBMM migration and differentiation, by regulating hsa-miR- 6727 - 5p/FBLN5. The area under curve (AUC) of the LINC01220/hsa-miR- 6727 - 5p/FBLN5 axis in diagnosing CAD was 0.954 (0.919-0.990), with sensitivity of 91.9% and specificity of 91.7%. LINC01220 may hinder CAD progression by negatively regulating hsa-miR- 6727 - 5p which targeted FBLN5, and they were potential biomarkers of CAD.

NASH poses a significant threat to human health and is recognized as the leading contributor to HCC. In this study, we leveraged publicly accessible datasets to identify novel differentially expressed genes that may serve as potential targets in NASH or potentially NASH-induced HCC. The publicly available datasets were obtained from the GEO. Differential gene expression analysis and enrichment analysis was performed. Subsequently, WGCNA and PPI network were constructed. Lastly, machine learning was employed to identify key feature genes. Utilizing the integrated GEO database, we identified 446 genes exhibiting differential expression. Enrichment analysis indicated that these genes are predominantly associated with glucose and lipid metabolism and inflammatory processes. Through WGCNA, three modules were identified that demonstrated a significant correlation with NASH. Furthermore, core genes among the differentially expressed genes were extracted via protein and protein interaction analysis. Ultimately, machine learning techniques were employed, leading to the identification of three genes: FosB, Fos, and SOCS3. Notably, FosB exhibited consistent expression across various datasets, demonstrated strong predictive capabilities for NASH, and was associated with improved prognostic outcomes in hepatocellular carcinoma by data from TCGA. Additionally, in vitro immunohistochemistry experiments revealed significant reduction of FosB expression in NASH. Bioinformatics analyses conducted on various datasets, along with in vitro immunohistochemistry experiments, revealed significant downregulation of FosB in NASH. It indicates that FosB plays a critical role in the pathogenesis of NASH, and its expression is associated with the prognosis of patients with HCC. Further experimental studies are required to investigate the potential targeting of FosB in NASH and NASH-induced HCC.

Common bean (Phaseolus vulgaris) anthracnose, caused by Colletotrichum lindemuthianum affects and decreases its yield substantially. Fifty Simple Sequence Repeat (SSR) markers were used to analyze the genetic and genotypic variation among 36 C. lindemuthianum isolates. Among the 50 SSRs, 24 were polymorphic and amplified 66 alleles. Most of the SSRs had polymorphic information content (PIC) values > 0.30, indicating their strong discriminative competence. Distance based dendrogram analysis and population structure analysis divided 36 C. lindemuthianum isolates into three clusters. Analysis of molecular variance at spatiotemporal levels showed high genetic variation among the populations. The six C. lindemuthianum subpopulations had high Shannon-Wiener indices. The multilocus genotype and genetic diversity indices show that C. lindemuthianum populations in Kashmir are diverse. The three geographic subpopulations of C. lindemuthianum rejected the null hypothesis of linkage equilibrium (p = 0.001). Before this study, all PCR based genetic diversity studies on C. lindemuthianum relied on dominant markers. This study is the first to identify 24 robust SSRs, which can be utilized to elucidate the population structure of the common bean anthracnose pathogen.