Biochemical Genetics最新文献

Dyslipidaemia, characterised by abnormal lipid levels in the blood, is an important risk factor for cardiovascular disease. In this case-control study, the association between single-nucleotide polymorphisms in ERBB2 and ERBB3 genes and the risk of dyslipidaemia in a population from Northern Anhui, China was evaluated. Particularly, we analysed samples from 543 patients with dyslipidaemia and 648 healthy controls for five potentially functional polymorphisms using TaqMan assays. Multivariate logistic regression was used to assess the relationship between genotype and dyslipidaemia, adjusting for confounding variables. The ERBB2 rs2517955 and rs1058808 single-nucleotide polymorphisms were significantly associated with dyslipidaemia. The rs2517955 variant showed a protective effect against dyslipidaemia in males, individuals aged 55 years or younger, and those without diabetes. Similarly, the rs1058808 variant decreased the risk of dyslipidaemia in these stratified groups. Conversely, ERBB3 rs2292238 was associated with an increased risk of dyslipidaemia in patients with diabetes. Compared with the corresponding wild-type alleles, variant alleles of rs2517955 and rs1058808 were associated with a reduced risk of decreased high-density lipoprotein cholesterol levels. Additionally, ERBB2 rs2517955 variants were significantly linked to total cholesterol levels, whereas ERBB3 rs3741499 and rs877636 variants were significantly associated with low-density lipoprotein cholesterol levels. Our findings suggest that ERBB2 and ERBB3 polymorphisms are closely associated with the risk of dyslipidaemia in the Chinese population. These results provide valuable insights for further genetic studies of dyslipidaemia and the identification of potential therapeutic targets.

Wilson disease is a rare monogenic disease characterized by copper overload in various organs, mainly the liver, the brain and the eyes. It has a prevalence ranging between 1/30,000 and 1/50,000, and it is caused by pathogenic variants in the ATP7B gene, which encodes a copper-transporting ATPase essential for regulating liver copper levels by directing copper to the secretory pathway and exporting excess copper into bile. It is a fatal disease if left untreated; however early diagnosis and effective treatment enable patient's outcome improvement. Unfortunately, in the Arab world there is no collective data on Wilson disease. This systematic review presents an explicit overview on the clinical and molecular spectrum of Wilson disease in the Arab world. A literature search was conducted on five databases from their inception until April 2024, using a combination of words related to the genetics of Wilson disease in the Arab world. The search resulted in 48 relevant studies carried out in 13 Arab countries, in which 802 Wilson disease patients were reported, with a high rate of consanguinity, and a slight male predominance. Hepatic presentations were the most frequent features in patients, and a total of 92 variants were identified with a detection rate of 61.2%. Genotype-phenotype correlations were not established for the majority of variants. This review revealed a clinical and molecular heterogeneity of Wilson disease in the Arab world. Efforts from health authorities, clinicians and geneticists are recommended to improve diagnosis, reduce disease incidence and give more insights into the present-day understanding of Wilson disease in the Arab world.

The high occurrence and death rates of colorectal cancer (CRC) make it a major health concern. Recent studies have identified NOP2/Sun RNA methyltransferase family member 2 (NSUN2), an RNA methyltransferase, as a key regulator in various tumor types. However, how exactly NSUN2-mediated m5C alteration affects CRC is still a mystery. This study seeks to understand how NSUN2 contributes to the growth and death of colorectal cancer cells. New tissue samples were taken in order to investigate NSUN2 expression in CRC. In vitro tests were performed to evaluate NSUN2's function. We used m5C-methylated-RNA immunoprecipitation and RNA stability experiments to find out how NSUN2 works on Solute carrier family 7 member 11 (SLC7A11, also called xCT). Downregulation of NSUN2 limits CRC cell growth and induces ferroptosis, as we show that NSUN2 was substantially expressed in CRC. In terms of the molecular mechanism, NSUN2 controls the translation and stability of SLC7A11 mRNA by regulating its m5C methylation. Functional tests show that SLC7A11 compensates for the NSUN2 knockdown-induced decrease in cell proliferation. Additionally, SLC7A11 overexpression restores ferroptosis to CRC cells after NSUN2 knockdown. These findings emphasize NSUN2's crucial role in modulating colorectal cancer cell growth and survival via SLC7A11, pointing to promising new therapeutic targets.

Betula utilis subsp. jacquemontii (Spach) Ashburner & McAll. is a medicinally and ecologically important tree species in the Western Himalayan Region (WHR) of India. Estimation of genetic variability and population structure of 11 populations of B. utilis subsp. jacquemontii in the WHR were carried out using 15 ISSR and 10 DAMD markers. The cumulative analyses of the markers (ISSR + DAMD) revealed a moderate level (49.47%) of polymorphism at the species level. Khilanmarg, Gangotri, and Khaliya top populations showed the highest polymorphism, while the Bhyundar Valley and Chatru-Kaza road populations showed the lowest polymorphism across 11 populations. Mantel test revealed a positive correlation between pair-wise genetic and geographical distances in wild populations of B. utilis subsp. jacquemontii in the WHR. The AMOVA analysis showed that majority of variation of the species exists among populations (54%), followed by within populations (20%). The clustering pattern obtained from UPGMA, PCoA, and STRUCTURE analyses revealed that 11 natural populations of B. utilis subsp. jacquemontii separated into two distinct genetic clusters. The genetic differentiation is notably high (G_ST = 0.74) among populations with a low gene flow (Nm = 0.16), which could be attributed to geographic isolation, high mountain ranges, regional climatic conditions, and habitat destruction in the WHR. The genetically diverse populations recognized in this study could be a valuable genetic resource for conservation and management of this important timberline tree species.

Epstein-Barr virus (EBV), the first human virus identified with oncogenic properties, encodes a class of microRNAs known as miR-BART (BamHI-A rightward transcript microRNAs). This study investigates the pivotal role of EBV-miR-BART14-3p in the progression of gastric cancer, particularly focusing on its effects on epithelial-mesenchymal transition (EMT), cell proliferation, and migration. EBV-associated gastric cancer (EBVaGC) is distinguished by unique genomic and epigenomic characteristics, with EBV miRNAs significantly influencing tumor biology by regulating gene expression. Our research demonstrates that EBV-miR-BART14-3p facilitates gastric cancer cell migration and invasion by targeting the tumor suppressor gene LACTB, which in turn activates the Phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, a critical driver of EMT. The suppression of LACTB in EBVaGC highlights its crucial role in inhibiting tumor progression. These findings position EBV-miR-BART14-3p as a key player in gastric cancer development and underscore its potential as both a prognostic biomarker and a therapeutic target for EBVaGC.

BRD4, part of the bromodomain and extra terminal domain (BET) protein family, plays a pivotal role in gene transcription, DNA replication, and repair via transcription regulators. Despite its established involvement in various human diseases, its function in esophageal squamous cell carcinoma (ESCC) has not been fully explored. Our research investigated the association of BRD4 in ESCC and its underlying molecular mechanisms. The findings revealed that BRD4 knockdown notably diminished the cells' proliferation, migration, invasion capabilities and induced apoptosis and cell cycle arrest. Conversely, overexpression of BRD4 can reverse these phenotypes. Pearson correlation and enrichment analyses indicated that BRD4 expression was associated with the cell cycle and Wnt/β-catenin signaling pathway. Further validation confirmed that reduced BRD4 expression downregulates Cyclin D1 and c-Myc, and suppresses epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin signaling pathway. Furthermore, rescue experiments showed that overexpressing c-Myc significantly mitigated the inhibitory impact of BRD4. Moreover, by employing single-cell transcriptome sequencing, we explored the impact of the tumor microenvironment on BRD4 overexpression in ESCC cells. These insights confirmed BRD4's potential as a therapeutic target, suggesting that modulating its expression could yield promising strategies for ESCC treatment.

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.

The predominant component of kidney stone is calcium oxalate monohydrate (COM), a fact widely acknowledged. Although rodent models are frequently used to induce calcium oxalate (CaOx) crystallization, further exploration of Randall's plaques (RPs) in these models is still needed. We first selected the GSE89028 and GSE75542 datasets from the Gene Expression Omnibus (GEO) database to identify commonly differentially expressed genes (co-DEGs). Based on co-DEGs, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify significantly enriched pathways. Additionally, we performed Gene Set Enrichment Analysis (GSEA) to validate the enriched pathways. In order to identify hub genes, we established a network of protein-protein interactions (PPI). Finally, we conducted real-time PCR and Western blot to validate the findings from the bioinformatics analysis. We selected 28 co-DEGs from two datasets. The enrichment analysis using GO, KEGG, and GSEA revealed significant enrichment of chemokine-related signaling pathways. The histogram analysis showed that three chemokine factor-related genes were involved in multiple pathways. We used Cytohubba to confirm the presence of three hub genes. Subsequently, analysis of external datasets and quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot demonstrated significant upregulation of CCL2, CXCL1, and CXCL2 in HK-2 cells following CaOx treatment compared to the control group (p < 0.05). Our study demonstrated that upon stimulation by CaOx, renal tubular epithelial cells release chemokines, including CCL2, CXCL1, and CXCL2. This release of chemokines is accompanied by the activation of signaling pathways such as TNF and IL-17. These findings may provide new directions for future research on Kidney Stone Disease.

Colorectal cancer (CRC) is the third most deadly cancer diagnosed in both men and women. 5-Fluorouracil (5-FU) treatment frequently causes the CRC cells to become chemoresistance, which has a negative impact on prognosis. Using bioinformatic techniques, this work describes important genes and biological pathways linked to 5-FU resistance in CRC cells. In our studies, a 5-FU-resistant HCT 116 cell line exhibiting elevated TYMS was created and validated using various tests. Bioinformatic studies were conducted to determine which differentially expressed genes (DEGs) were responsible for the establishment of 5-FU resistance in the same cell line. After screening 3949 DEGs from the two public datasets (GSE196900 and GSE153412), 471 overlapping DEGs in 5-FU-resistant HCT 116 cells were chosen. These overlapping DEGs were used to build the PPI network, and a major cluster module containing 21 genes was found. Subsequently, using three topological analysis algorithms, 10 hub genes were identified, which included HLA-DRA, HLA-DRB1, CXCR4, MMP9, CDH1, SMAD3, VIM, SYK, ZEB1, and SELL. Their roles were ascertained by utilizing Gene Ontology keywords and pathway enrichment studies. Our results also demonstrated that the miRNA and transcription factors (TFs) that had the strongest connection with the hub genes were hsa-mir-26a-5p, hsa-mir-30a-5p, RELA, and NFKB1. Ultimately, 84 FDA-approved drugs that target those hub genes were found to potentially treat 5-FU resistance CRC. Our research's findings increase our understanding of the fundamental factors that contribute to the prevalence of 5-FU resistance CRC, which could ultimately assist in the identification of valuable malignancy biomarkers and targeted treatment approaches based on key regulatory pathways.