Biochemical Genetics最新文献

The genus Babylonia, classified under Mollusca, Gastropoda, Neogastropoda, has been a subject of controversy concerning the phylogenetic relationships within Neogastropoda, a highly intricate group of predatory marine snails. In this study, we sequenced complete mitogenomes of Babylonia spirata and Babylonia zeylanica. Both mitogenomes consist of 37 genes, including 13 PCGs, 22 tRNAs, and 2 rRNAs, which is consistent with the gene numbers observed in most neogastropod snails. We analyzed base content, codon usage preference, and tRNA structure to describe the basic structural features. Additionally, phylogenetic trees were constructed using Maximum Likelihood and Bayesian Inference based on the complete mitogenomes of 43 Neogastropoda species. This analysis revealed that all 19 families formed monophyletic groups, collectively constituting seven monophyletic superfamilies. Moreover, by analyzing the gene arrangement characteristics of these 43 Neogastropoda species, we identified four distinct types of mitochondrial genome arrangements. This study strongly supports the monophyly of Neogastropoda families, contradicting previous molecular studies and providing fundamental insights for further phylogenetic studies in Neogastropoda.

Breast cancer is one of the most prevalent cancers globally and remains a significant cause of cancer-related mortality among women despite advancements in early detection and treatment. The heterogeneity of breast cancer arises from a complex interplay of genetic and environmental factors. Early-stage breast cancer is often asymptomatic, with initial signs including subtle changes in breast morphology and localized swelling, emphasizing the need for reliable diagnostic tools for early detection. Recent research has highlighted the potential of molecular biomarkers, particularly non-coding RNAs such as circular RNAs (circRNAs), in cancer diagnosis. CircRNAs, a unique subset of non-coding RNAs, are characterized by their covalently closed-loop structure, which confers exceptional stability and resistance to exonuclease degradation. They are present in various body fluids and have demonstrated regulatory roles in transcription, translation, and as microRNA sponges, making them promising candidates for cancer diagnostics and prognostics. This study focuses on evaluating the diagnostic potential of two circRNAs, hsa_circ_0001666 and hsa_circ_0003227, by examining their expression in normal, tumor, and metastatic breast cancer cell lines. Breast cancer cell lines representing normal (MCF-10A), tumor (MCF-7), and metastatic (BT-20) stages were cultured for analysis. Total RNA was extracted using a column-based RNA extraction kit, and RNA quality was assessed through NanoDrop spectrophotometry and agarose gel electrophoresis. Complementary DNA (cDNA) synthesis was performed using random hexamers, and the expression levels of hsa_circ_0001666 and hsa_circ_0003227 were quantified using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR), with beta-actin serving as the internal control. Statistical analyses were conducted using SPSS software to evaluate differences in expression levels across cell lines. A significant downregulation of hsa_circ_0001666 and hsa_circ_0003227 was observed in tumor and metastatic cell lines compared to normal breast cell lines (P < 0.05). These results suggest that the expression of these circRNAs correlates with the progression of breast cancer, with decreased levels observed as cells transition from normal to tumorigenic and metastatic stages. The findings of this study indicate that hsa_circ_0001666 and hsa_circ_0003227 have potential utility as diagnostic biomarkers for breast cancer. Their significant expression changes across different stages of breast cancer highlight their relevance in early detection and disease monitoring. This study reinforces the potential of RNA-based biomarkers, particularly circRNAs, in cancer diagnosis and treatment. However, in vitro findings require validation in clinical samples and larger cohorts. Future research should explore their roles in breast cancer progression and integration into non-invasive diagnostics.

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.

Breast invasive carcinoma (BRCA) affects women worldwide, and despite advancements in diagnosis, prevention, and treatment, outcomes remain suboptimal. TNIP1, a novel target involved in multiple immune signaling pathways, influences tumor development and survival. However, the connection between BRCA and TNIP1 remains unclear. Analysis of data from the TCGA, GEO, Sangerbox, and Ualcan databases revealed that TNIP1 is underexpressed in BRCA tissues. This finding was corroborated by RT-PCR and immunohistochemistry. Furthermore, data from the TCGA and GEPIA2 databases, along with Sangerbox, identified TNIP1 as a marker of poor prognosis in BRCA patients. TNIP1 expression shows significant positive correlations with the BRCA Tumor Microenvironment (TME) StromalScore (R = 0.22), ImmuneScore (R = 0.25), and ESTIMATEScore (R = 0.27). Various algorithms have demonstrated a strong association between TNIP1 expression and BRCA tumor-infiltrating immune cells (TIICs). Further analysis using EPIC, TIMER, MCPCounter, QUANTISEQ, xCell, and other computational tools revealed that elevated TNIP1 expression is significantly associated with increased immune cell scores. TNIP1 expression in BRCA tumor tissues also shows a strong correlation with immune checkpoint markers. Data from the HAP database indicate that TNIP1 expression is predominantly involved in the normal skin microenvironment. Subsequent analysis using the TISCH platform with the BRCA single-cell dataset demonstrated that TNIP1 exhibits higher expression levels in immune cells compared to non-immune cells in BRCA patients. This expression is significantly positively correlated with inflammation (R = 0.25) and differentiation (R = 0.28) within the TME, while showing negative correlations with BRCA stemness (R = - 0.34) and invasion (R = - 0.22). Consequently, TNIP1 is proposed as a potential prognostic marker and therapeutic target for BRCA.

Amelogenesis Imperfecta (AI) is a set of hereditary diseases affecting enamel development, leading to various types of enamel defects, potentially impacting oral health unassociated with other generalized defects. AI manifests in syndromic and non-syndromic forms and can be inherited through autosomal recessive, autosomal dominant, or X-linked inheritance patterns. Genetic studies have identified sequence variants in a number of genes (≥ 70) linked to both syndromic and non-syndromic AI, highlighting the genetic diversity underlying the condition. The current study involved clinical evaluation and exome sequencing, aimed at identifying the causative variants in four unrelated consanguineous Pakistani families presenting AI phenotypes. The exome sequencing results revealed a novel homozygous frameshift variant FAM20A: NM_017565.4, c.188dupA; p.(Asp63Glufs*17) in families A, B, and C while a nonsense homozygous variant WDR72: NM_182758.4, c.2686C > T; p. (Arg896*) in family D. The segregation of both variants was confirmed by Sanger sequencing. Bioinformatics analysis predicted the pathogenicity of these genetic variants. These alterations suggest functional consequences, potentially impairing the FAM20A and WDR72 proteins and causing dental anomalies. This investigation significantly broadens our understanding of FAM20A and WDR72's involvement in AI. Furthermore, this study highlights the genetic heterogeneity of AI (involving FAM20A and WDR72 in this study) within the Pakistani population.

Breast cancer is the most common invasive cancer diagnosed in females and is also the main cause of cancer-related deaths leading to more than 500,000 deaths annually. The present study aims to identify a promising panel of microRNAs (miRNAs) using bioinformatics analysis, and to clinically validate their utility for diagnosing breast cancer patients with high accuracy in a clinical setting. First, in the in silico phase of our study, using bioinformatics analysis and the data available in the GEO database, miRNAs that were increased in the interstitial fluid of the tumor tissues (differentially expressed miRNAs), were screened and their related target genes were selected. Multimir package of R software was utilized to determine the target genes of the differentially expressed miRNAs (DEMs). The biological functions of discovered genes were analyzed using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In order to determine the molecular mechanisms behind important signaling pathways and cellular functions, the protein-protein interaction network was built using STRING and Cytoscape software. After that, in the laboratory phase, the expression level of three candidate miRNAs on the serum samples of 26 breast cancer patients and 26 control, as well as 14 tumor tissue samples and 14 adjacent normal tissue samples, has been investigated by Real-time PCR method. Then sensitivity and specificity of candidate miRNAs were evaluated through the ROC curve analysis. After in silico analysis, we revealed that three miRNAs including miR-4443, miR-572, and miR-150-5p were highly increased in the interstitial fluid of breast cancer patients compared to breast cancer tissues. Moreover, our results revealed that the expression level of miR-4443, miR-572, and miR-150-5p were significantly decreased in the serum of breast cancer patients compare to normal controls. Also, the expression level of miR-4443 and miR-150-5p was significantly decreased in the tumor tissue compared to the adjacent non-tumor tissue. Also, ROC curve analysis showed that these three miRNAs have high sensitivity and specificity for the diagnosis of breast cancer patients. Data analysis was conducted with GraphPad Prism software. Our findings suggest the potential utility of measuring tumor-derived miRNAs in serum as an important approach for the blood-based detection of breast cancer patients. It appears that miR-4443, miR-572, and miR-150-5p may serve as promising diagnostic biomarkers with high sensitivity and specificity. However, it's important to note that further research will be needed to definitively establish the use of these miRNAs as potential biomarkers in clinical practice.

Rhinogobius zhoui is found only in streams on Lianhua Mountain, Guangdong Province, China. Juveniles of Rhinogobius zhoui bred in an artificial environment do not undergo a planktonic period and have a landlocked life history. At present, there is not much published literature regarding this species. To study the structural characteristics and phylogenetic information of the mtDNA of Rhinogobius zhoui, the mtDNA of R. zhoui was obtained by next-generation sequencing. The mtDNA was assembled, annotated, and analyzed using a bioinformatics method, followed by alignment of mtDNA and analysis of sequence differences. R. zhoui was analyzed phylogenetically using data on 48 species of Gobiiformes and 2 species of Cypriniformes downloaded from NCBI ( https://www.ncbi.nlm.nih.gov/ ), and phylogenetic trees were generated using maximum likelihood and Bayesian inference. The results of our analysis showed that (1) the length of the mtDNA of R. zhoui was 16,491 bp, according to next-generation sequencing and its mitochondrial structure included 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one non-coding region and (2) from the phylogenetic tree thus generated, it can be seen that R. zhoui and Rhinogobius duospilus are closely related. This study will re-examine the Phylogenetic tree of the major lineages in Gobiiformes.

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.