Search Results (6)

Background: Altered gene expression in cancers holds great potential to improve the diagnostics and differentiation of primary and metastatic liver cancers. In this study, the expression of the protein-coding genes ring finger protein 135 (RNF135), ephrin-B2 (EFNB2), ring finger protein 125 (RNF125), homeobox-C 4 (HOXC4), actin-binding LIM protein 1 (ABLIM1) and oncostatin M receptor (OSMR) and the long non-coding RNAs (lncRNA) prospero homeobox 1 antisense RNA 1 (PROX1-AS1) and leukemia inhibitory factor receptor antisense RNA 1 (LIFR-AS1) was investigated in hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastases and pancreatic ductal adenocarcinoma liver metastases. Methods: This study included 149 formalin-fixed, paraffin-embedded samples from 80 patients. After RNA isolation, quantification, reverse transcription and preamplification, real-time qPCR was performed. The gene expression between different groups was calculated relative to the expression of the reference genes using the ∆∆Cq method and statistically analyzed. The expression of the genes was additionally analyzed using the AmiCA and UCSC Xena platforms. Results: In primary cancers, our results showed differential expression between primary tumors and healthy tissues for all the genes and lncRNA examined. Moreover, we found downregulation of RNF135 in hepatocellular carcinoma, downregulation of OSMR in colorectal liver metastases and upregulation of HOXC4 in cholangiocarcinoma compared to primary liver cancers and metastatic cancers. The major finding is the upregulation of ABLIM1 in cholangiocarcinoma compared to hepatocellular carcinoma, colorectal liver metastases, pancreatic ductal adenocarcinoma liver metastases and healthy liver tissue. We propose ABLIM1 as a potential biomarker that differentiates cholangiocarcinoma from other cancers and healthy liver tissue. Conclusions: This study emphasizes the importance of understanding the differences in gene expression between healthy tissues and primary and metastatic cancers and highlights the potential use of altered gene expression as a diagnostic biomarker in these malignancies. Full article

Osteosarcoma (OS) is a common bone malignancy in children and adolescents. Although histological subtyping followed by improved OS treatment regimens have helped achieve favorable outcomes, a lack of understanding of the molecular subtypes remains a challenge to characterize its genetic heterogeneity and subsequently to identify diagnostic and prognostic biomarkers for developing effective treatments. In the present study, global analysis of DNA methylation, and mRNA and miRNA gene expression in OS patient samples were correlated with their clinical characteristics. The mucin family of genes, MUC6, MUC12, and MUC4, were found to be highly mutated in the OS patients. Results revealed the enrichment of molecular pathways including Wnt signaling, Calcium signaling, and PI3K-Akt signaling in the OS tumors. Survival analyses showed that the expression levels of several genes such as RAMP1, CRIP1, CORT, CHST13, and DDX60L, miRNAs and lncRNAs were associated with survival of OS patients. Molecular subtyping using Cluster-Of-Clusters Analysis (COCA) for mRNA, lncRNA, and miRNA expression; DNA methylation; and mutation data from the TARGET dataset revealed two distinct molecular subtypes, each with a distinctive gene expression profile. Between the two subtypes, three upregulated genes, POP4, HEY1, CERKL, and seven downregulated genes, CEACAM1, ABLIM1, LTBP2, ISLR, LRRC32, PTPRF, and GPX3, associated with OS metastasis were found to be differentially regulated. Thus, the molecular subtyping results provide a strong basis for classification of OS patients that could be used to develop better prognostic treatment strategies. Full article

The intuitive impression of pork is extremely important in terms of whether consumers are enthusiastic about purchasing it. Flesh color and intramuscular fat (IMF) are indispensable indicators in meat quality assessment. In this study, we determined the flesh color and intramuscular fat at 45 min and 12 h after slaughter (45 mFC, 45 mIMF, 12 hFC, and 12 hIMF) of 1518 commercial Duroc × Landrace × Large White (DLY) pigs. We performed a single nucleotide polymorphism (SNP) genome-wide association study (GWAS) analysis with 28,066 SNPs. This experiment found that the correlation between 45 mFC and 12 hFC was 0.343. The correlation between 45 mIMF and 12 hIMF was 0.238. The heritability of the traits 45 mFC, 12 hFC, 45 mIMF, and 12 hIMF was 0.112, 0.217, 0.139, and 0.178, respectively, and we identified seven SNPs for flesh color and three SNPs for IMF. Finally, several candidate genes regulating these four traits were identified. Three candidate genes related to flesh color were provided: SNCAIP and PRR16 on SSC2, ST3GAL4 on SSC5, and GALR1 on SSC1. A total of three candidate genes related to intramuscular fat were found, including ABLIM3 on SSC2, DPH5 on SSC4, and DOCK10 on SSC15. Furthermore, GO and KEGG analysis revealed that these genes are involved in the regulation of apoptosis and are implicated in functions such as pigmentation and skeletal muscle metabolism. This study applied GWAS to analyze the scoring results of flesh color and IMF in different time periods, and it further revealed the genetic structure of flesh color and IMF traits, which may provide important genetic loci for the subsequent improvement of pig meat quality traits. Full article

Numerous cardiovascular diseases (CVD) eventually lead to severe myocardial dysfunction, which is the most common cause of death worldwide. A better understanding of underlying molecular mechanisms of cardiovascular pathologies seems to be crucial to develop effective therapeutic options. Therefore, a worthwhile endeavor is a detailed molecular characterization of cells extracted from the myocardium. A transcriptomic profile of atrial cardiomyocytes during long-term primary cell culture revealed the expression patterns depending on the duration of the culture and the heart segment of origin (right atrial appendage and right atrium). Differentially expressed genes (DEGs) were classified as involved in ontological groups such as: “cellular component assembly”, “cellular component organization”, “cellular component biogenesis”, and “cytoskeleton organization”. Transcriptomic profiling allowed us to indicate the increased expression of COL5A2, COL8A1, and COL12A1, encoding different collagen subunits, pivotal in cardiac extracellular matrix (ECM) structure. Conversely, genes important for cellular architecture, such as ABLIM1, TMOD1, XIRP1, and PHACTR1, were downregulated during in vitro culture. The culture conditions may create a favorable environment for reconstruction of the ECM structures, whereas they may be suboptimal for expression of some pivotal transcripts responsible for the formation of intracellular structures. Full article

Zinc fingers consist of one of the most abundant motifs in transcription factors and DNA-binding proteins. Recent studies provide evidence on the pathological implication of zinc finger proteins in various neurodevelopmental disorders and malignancies but their role in pediatric brain tumors is largely unexplored. To this end, we investigated the differential expression of zinc finger-containing genes along with relevant biological processes and pathways among four main brain tumor categories (pilocytic astrocytomas, ependymomas, medulloblastomas and glioblastomas). By employing an extended bioinformatic toolset, we performed a preliminary in silico study in order to identify the expression of zinc finger-containing genes and associated functions in pediatric brain tumors. Our data analysis reveals the prominent role of C₂H₂-type zinc finger-containing genes in the molecular mechanisms underlying pediatric brain tumors followed by the Ring and PHD finger types. Significant dysregulation of ABLIM2 and UHFR1 genes was detected in all tumor types drawing attention to the dysregulation of cell polarization process and Ubiquitin-Proteasome System (UPS) in the pathogenesis of pediatric brain tumors. Moreover, significant gene clustering was observed in multiple locations with two highly visible clusters revealing a contrast in gene regulation between medulloblastomas and the other three brain tumor types, indicating a promising area of future research. Full article

Prolonged use of opioids can cause opioid-induced hyperalgesia (OIH). The impact of alternative splicing on OIH remains partially characterized. A study of the absolute and relative modes of action of alternative splicing further the understanding of the molecular mechanisms underlying OIH. Differential absolute and relative isoform profiles were detected in the trigeminal ganglia and nucleus accumbens of mice presenting OIH behaviors elicited by chronic morphine administration relative to control mice. Genes that participate in glutamatergic synapse (e.g., Grip1, Grin1, Wnk3), myelin protein processes (e.g., Mbp, Mpz), and axon guidance presented absolute and relative splicing associated with OIH. Splicing of genes in the gonadotropin-releasing hormone receptor pathway was detected in the nucleus accumbens while splicing in the vascular endothelial growth factor, endogenous cannabinoid signaling, circadian clock system, and metabotropic glutamate receptor pathways was detected in the trigeminal ganglia. A notable finding was the prevalence of alternatively spliced transcription factors and regulators (e.g., Ciart, Ablim2, Pbx1, Arntl2) in the trigeminal ganglia. Insights into the nociceptive and antinociceptive modulatory action of Hnrnpk were gained. The results from our study highlight the impact of alternative splicing and transcriptional regulators on OIH and expose the need for isoform-level research to advance the understanding of morphine-associated hyperalgesia. Full article