Comparative and Functional Genomics最新文献

Cell division cycle 25B (CDC25B), a member of the CDC25 phosphatase family, plays a key role in cell cycle regulation. Studies have suggested its carcinogenic potential in various cancers, but the role of CDC25B in the development of hepatocellular carcinoma (HCC) remains poorly understood. The aim of this study was to clarify the role of CDC25B in HCC using bioinformatics and experiments. CDC25B expression data of HCC cancer tissues and paracancerous normal samples were obtained from The Cancer Gene Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the relationship between CDC25B expression and the prognosis and degree of tumor differentiation of HCC patients was analyzed. CDC25B expression was verified in clinical HCC tissue samples using fluorescence quantitative polymerase chain reaction (q-PCR) and protein immunoblotting (Western blot). Gene set enrichment analysis (GSEA) was used to identify signaling pathways enriched in CDC25B expression, and differential genes (DEGs) were used to screen out coexpressed hub genes and construct protein-protein interaction (PPI) networks. 5-Ethynyl-2 ^′-deoxyuridine (EDU) staining was used to compare the proliferation and differentiation ability of the HCC cell line (HCC-LM3) after knockdown of CDC25B. Finally, we investigated the mutation of CDC25B in HCC and the relationship between CDC25B expression and tumor cell infiltration of lymphocytes and some immune checkpoints as well as drug sensitivity. CDC25B was overexpressed in HCC tissues and correlated with poor prognosis and the degree of tumor differentiation in patients with HCC. The GSEA and PPI networks together revealed significantly upregulated signaling pathways, as well as functions, associated with the development of HCC when CDC25B was overexpressed. The EDU assay demonstrated that the ability of cells to differentiate value addedly was markedly reduced following the downregulation of CDC25B expression in HCC-LM3s. CDC25B was also involved in the formation of the tumor microenvironment (TME) and immune processes in HCC, and the high expression of CDC25B made patients less sensitive to some drugs. CDC25B can be used as a biomarker and immunotherapeutic target for poor prognosis and partial drug sensitivity in HCC, providing new ideas for HCC treatment.

SQUAMOSA promoter-binding protein-like (SPL) gene family, a group of plant-specific transcription factors, played crucial roles in regulating plant growth, development, signal transduction, and stress response. This study focuses on the SPL gene family in the fast-growing Eucalyptus grandis, employing bioinformatics approaches to identify and analyze the gene physiochemical characteristics, conserved domains, structural composition, chromosomal distribution, phylogenetic relationships, cis-acting elements, and their expression patterns in various tissues and stress treatments. Twenty-three SPL genes were identified in E. grandis, which uneven distributed across seven chromosomes and classified into five groups. Prediction of cis-acting elements revealed that these genes might be related to light, hormone, and stress responses. Furthermore, EgSPL9 and EgSPL23, mainly expressed in the stem apex and lateral branches, seem to be involved in hormone stress resistance. Our study provides insights into the potential functions of the EgSPL genes in plant growth, stress response, and hormone transduction, offering valuable perspectives for subsequent research into their biological roles.

Aims: Exploring key genes and potential molecular pathways of ferroptosis in immunoglobulin A nephropathy (IgAN).

Methods: The IgAN datasets and ferroptosis-related genes (FRGs) were obtained in the Gene Expression Omnibus (GEO) and FerrDb database. Differentially expressed genes (DEGs) were identified using R software and intersected with FRGs to obtain differentially expressed FRGs (DE-FRGs). After that, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis (PEA) and Gene Ontology (GO) functional annotation were performed on DE-FRGs. In the Search Tool for the Retrieval of Interacting Genes (STRING) website, we construct a protein–protein interaction (PPI) network. The PPI network was further investigated with screening hub genes with Cytoscape software. The core genes were then subjected to gene set enrichment analysis (GSEA). Finally, the samples were analyzed for immune infiltration in R, and the correlation between hub genes and immune cells was analyzed.

Results: A total of 347 DEGs were identified. CD44, CDO1, CYBB, IL1B, RRM2, AKR1C1, activated transcription factor-3 (ATF3), CDKN1A, GDF15, JUN, MGST1, MIOX, MT1G, NR4A1, PDK4, TNFAIP3, and ZFP36 were determined as DE-FRGs. JUN, IL1B, and ATF3 were then screened as hub genes. GSEA and immune infiltration analysis revealed that the hub genes were closely associated with immune inflammatory responses such as NOD-like receptor signaling, IL-17 signaling, and TNF signaling.

Conclusions: Our results show that JUN and ATF3 are possibly critical genes in the process of IgAN ferroptosis and may be related with immune cell infiltration.

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor primarily occurring in the abdominopelvic region of young patients, and it is characterized by spindle-shaped myofibroblasts, or fibroblasts surrounded by inflammatory infiltrate. Herein, we report a case of a 24-year-old male with a firm submucosal mass in the anterior right vocal fold diagnosed as an IMT that recurred 14 months later. The tumor demonstrated a novel THBS1::ALK fusion containing Exons 1–7 of the thrombospondin 1 (THBS1) gene fused to Exon 19 of the anaplastic lymphoma kinase (ALK) gene via next-generation sequencing with the NextSeq sequencer. The fusion of THBS1 to ALK potentially results in increased expression and constitutive activation of the ALK kinase domain. These findings not only broaden the repertoire of known ALK fusion partners implicated in tumorigenesis but also provide a novel avenue for investigating the etiology of recurrent IMT by considering this fusion event as a causal factor. To our knowledge, this is the second case of IMT of the larynx with this novel mutation reported in the literature and the first such case with a detailed description of this specific fusion and clinical recurrence.

Calcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store-operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on a variety of cancer cell lines. The objective of this study was to investigate the anticancer effect of SKF96365 on esophageal cancer in vivo and in vitro. Cell Counting Kit-8 (CCK-8) and colony formation were used to test the proliferation inhibition of SKF96365 on cell lines. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect cell apoptosis rates. In addition, we demonstrated the antitumor effect of SKF96365 in vivo in xenografted mice. As a result, SKF96365 significantly inhibited the proliferation of K510, K30, and EC9706 in vitro. SKF96365 induces apoptosis in three cell lines through the poly(adenosine diphosphate–ribose) polymerase (PARP), caspase-9, and BCL-2 pathways in a dose-dependent and time-dependent manner. Moreover, SKF96365 treatment also induced apoptosis and inhibited tumor growth in nude mice. The calcium channel TRPC1 was significantly downregulated by SKF96365. Autophagy was also induced during the treatment of SKF96365. In summary, SKF96365 induces apoptosis (PARP, caspase-9, and BCL-2) and autophagy (LC3-A/B) by inhibiting TRPC1 in esophageal cancer cells, thereby inhibiting tumor growth.

Background: Progressive myoclonus epilepsy (PME) is a neurodegenerative disorder marked by recurrent seizures and progressive myoclonus. To date, based on the phenotypes and causal genes, more than 40 subtypes of PMEs have been identified, and more remain to be characterized. Our study is aimed at identifying the aberrant gene(s) possibly associated with PMEs in two siblings born to asymptomatic parents, in the absence of known genetic mutations.

Methods: Clinical assessments and molecular analyses, such as the repeat expansion test for CSTB; SCA1, 2, 3, 6, and 7; whole exome sequencing (WES); and mitochondrial genome sequencing coupled with computational analysis, were performed.

Results: A family-based segregation analysis of WES data was performed to identify novel genes associated with PMEs. The potassium channel, KCNH8 [c.298T>C; (p.Tyr100His)], a DNA repair gene, regulator of telomere elongation helicase 1 (RTEL1) [c.691G>T; (p.Asp231Tyr)] and long noncoding RNA, RTEL1-TNFRSF6B [chr20:62298898_G>T; NR_037882.1, hg19] were among the candidate genes that were found to be associated with PMEs. These homozygous variations in siblings belong to genes with a loss-of-function intolerant (pLI) score of ≤ 0.86, expected to be detrimental by multiple computational analyses, and were heterozygous in parents. Additionally, computational analysis and the expression of RTEL1 and RTEL1-TNFRSF6B revealed that RTEL1-TNFRSF6B may modulate RTEL1 via hsa-miR-3529-3p. In the patient with the severe phenotype, a further deleterious mutation in SLC22A17 was identified. No de novo variants specific to these probands were identified in the mitochondrial genome.

Conclusions: Our study is the first to report variants in KCNH8, RTEL1, and RTEL1-TNFRSF6B among PME cases. These genes when characterized fully may shed light on pathogenicity and have the potential to be used in the diagnosis of PME.

Bacterial strains coded 21LM367, 21LM07, and 21LM1136 were isolated from the urine of patients with urinary tract infections (UTIs) at the Centre Hospitalier Régional de Daloa in Côte d’Ivoire. Based on average nucleotide identity (ANI) analysis, DNA-DNA digital hybridisation (dDDH), and other comparative genomic methods, strains 21LM07, 21LM367, and 21LM1136 were determined to be Priestia flexa. The size of the assembled complete genomes ranged from 8,624,538 to 4,007,501 bp. The average GC content was 37.76%, 46.33%, and 43.03% for strains 21LM07, 21LM367, and 21LM1136, respectively. The total number of coding regions (CDS) in each genome was 4172, 8497, and 6795, respectively, for strains 21LM07, 21LM367, and 21LM1136. Genomic prediction analysis revealed that a total of 4241, 8583, and 6881 genes were annotated in the 21LM07, 21LM367, and 21LM1136 genomes, respectively. No virulence or resistance genes were predicted in the genomes of strains 21LM07 and 21LM1136. On the other hand, two genes conferring resistance to beta-lactam and tetracyclines as well as nine virulence genes were predicted in the genome of 21LM367. In addition, 438, 350, and 153 mobile genetic elements (MGEs) were predicted in the genomes of strains 21LM367, 21LM1136, and 21LM07, respectively. Strain 21LM07 was characterised by the absence of plasmids in its genome. Two plasmids were predicted in the genomes of isolates 21LM367 and 21LM1136; however, rep7a and IncI2 were predicted to contain the tet(K) resistance gene. No typical multilocus sequences could be characterised in the genomes of the different strains.

The seeds of Camellia oleifera produce high amount of oil, which can be broadly used in the fields of food, industry, and medicine. However, the molecular regulation mechanisms of seed development and oil accumulation in C. oleifera are unclear. In this study, evolutionary and expression analyses of the MADS-box gene family were performed across the C. oleifera genome for the first time. A total of 86 MADS-box genes (ColMADS) were identified, including 60 M-type and 26 MIKC members. More gene duplication events occurred in M-type subfamily (6) than that in MIKC subfamily (2), and SEP-like genes were lost from the MIKC^C clade. Furthermore, 8, 15, and 17 differentially expressed ColMADS genes (DEGs) were detected between three developmental stages of seed (S1/S2, S2/S3, and S1/S3), respectively. Among these DEGs, the STK-like ColMADS12 and TT16-like ColMADS17 were highly expressed during the seed formation (S1 and S2), agreeing with their predicted functions to positively regulate the seed organogenesis and oil accumulation. While ColMADS57 and ColMADS07 showed increasing expression level with the seed maturation (S2 and S3), conforming to their potential roles in promoting the seed ripening. In all, these results revealed a critical role of MADS-box genes in the C. oleifera seed development and oil accumulation, which will contribute to the future molecular breeding of C. oleifera.

Objective: The present study is aimed at introducing and evaluating MaterniCode, a state-of-the-art bioinformatic pipeline for noninvasive prenatal testing (NIPT) that leverages the Ion Torrent semiconductor sequencing platform. The initiative strives to revolutionize prenatal diagnostics by offering a rapid and cost-effective method without sacrificing accuracy.

Methods: Two distinct bioinformatic strategies were employed for fetal sex determination, one of which achieved 100% accuracy. We analyzed 1225 maternal blood samples for fetal aneuploidies, benchmarking against the industry standard Illumina VeriSeq™ NIPT Solution v2. The capability of MaterniCode to detect and characterize complex chromosomal anomalies was also assessed.

Results: MaterniCode achieved near-perfect accuracy in fetal sex determination through chromosome Y (chrY )–specific gene analysis, whereas the alternative method, employing the ratio of high-quality mapped reads on chrY relative to all reads, delivered 100% accuracy. For fetal aneuploidy detection, both the integrated WisecondorX and NIPTeR algorithms demonstrated a 100% sensitivity and specificity rate, consistent with Illumina VeriSeq™ NIPT Solution v2. The pipeline also successfully identified and precisely mapped significant chromosomal abnormalities, exemplified by a 2.4 Mb deletion on chromosome 13 and a 3 Mb duplication on chromosome 2.

Conclusion: MaterniCode has proven to be an innovative and highly efficient tool in the domain of NIPT, demonstrating excellent sensitivity and specificity. Its robust capability to effectively detect a wide range of complex chromosomal aberrations, including rare and subtle variations, positions it as a promising and valuable addition to prenatal diagnostic technologies. This enhancement to diagnostic precision significantly aids clinicians in making informed decisions during pregnancy management.