Comparative and Functional Genomics最新文献

Background: Helicobacter pylori (HP) is associated with the development of various stomach diseases, one of the major risk factors for stomach adenocarcinoma (STAD).

Methods: The HP infection score between tumor and normal groups was compared by single-sample gene set enrichment analysis (ssGSEA). The key modules related to HP infection were identified by weighted gene coexpression network analysis (WGCNA), and functional enrichment analysis was conducted on these module genes. Further, the limma package was used to screen the differentially expressed genes (DEGs) between HP-positive and HP-negative STAD. The prognostic genes were obtained to construct the riskscore model, and the performance of the model was validated. The correlation between riskscore and tumor immune microenvironment (TIME) was analyzed by Spearman’s method. The single-cell atlas of HP-positive STAD was delineated. The mRNA expression levels of the prognostic genes were verified using STAD cells, and the migration and invasion capacities of STAD cells were evaluated by using the wound healing assay and transwell assay.

Results: The HP infection score in the tumor group was significantly higher than that in the normal group. The purple and royal blue modules showed higher correlation with HP infection in STAD, and these module genes were enriched in the immune-related pathway. Further, five prognostic genes (CTLA4, CPVL, EMB, CXCR4, and FAM241A) were screened from the HP infection–related DEGs, which were utilized for establishing the riskscore model, with good robustness. Riskscore exhibited strong correlation with TIME in STAD. Single-cell atlas of HP-positive STAD revealed that CXCR4 is highly expressed in Epithelial Cell 1, Epithelial Cell 2, and parietal cells of the tumor group. CPVL, EMB, CTLA4, FAM241A, and CXCR4 showed high expression in STAD cells, and the silencing of CPVL could suppress the migration and invasion of STAD cells.

Conclusion: This study established a riskscore model based on HP infection–related genes, which could provide reference for prognostic prediction and treatment targets of STAD.

Background: Recently, exportin gene family members have been demonstrated to play essential roles in tumor progression. However, research on the clinical significance of exportin gene family members is limited in clear cell renal cell carcinoma (ccRCC).

Methods: Pan-cancer data, ccRCC multiomics data, and single-cell sequence were included to analyze the differences in DNA methylation modification, single nucleotide variations (SNVs), copy number variations (CNVs), and expression levels of exportin gene family members. Non-negative matrix factorization was used to identify molecular subtypes based on exportin gene family members, and the prognostic and biological differences of different molecular subtypes were compared across multiple dimensions.

Results: Exportin gene family members were upregulated in pan-cancer expression, and their aberrant expression was significantly influenced by DNA methylation, SNV, and CNV, particularly in ccRCC. Based on the expression matrix of exportin gene family members, two molecular subtypes, exportin famliy genes (XPO)–based subtype 1 (XPS1) and exportin famliy genes (XPO)–based subtype 2 (XPS2), were identified. The expression levels of exportin gene family members in the XPS2 subtype were significantly higher than those in XPS1, and the prognosis was poorer. The XPS2 subtype had lower immune component abundance and higher immune exhaustion scores. Its response rate to immunotherapy was significantly lower than that of the XPS1 subtype, but it was more sensitive to small molecules, including mercaptopurine and nutlin. Among them, exportin-1 (XPO1) is a potential diagnostic and therapeutic target for ccRCC, which can promote renal cancer progression by activating the PI3K-AKT-mTOR (phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mechanistic target of rapamycin (MTOR)) and interferon alpha pathways.

Conclusion: This study analyzed the variations of exportin gene family members at the pan-cancer level and identified two distinct ccRCC subtypes, which can guide personalized management of patients.

Red raspberry (Rubus idaeus L.), which is an important nutritional source for human health, belongs to fruit crops of the Rosaceae family. Here, we used Pacific Biosciences single-molecule real-time (SMRT) sequencing and high-throughput chromosome conformation capture (Hi-C) sequencing technologies to assemble genomes and reported a high-quality Rubus idaeus L. (DNS-1) genome with 321.29 Mb assembled into seven chromosomes. The LAI score of the DNS-1 genome assembly was 21.32, belonging to gold quality. Approximately 52.3% of the assembly sequences were annotated as repetitive sequences, and 24.15% were composed of long terminal repeat elements. A total of 29,814 protein-coding genes and 2474 pseudogenes were predicted in DNS-1. We characterized the complete genomes of DNS-1 and compared them to those of seven other species. We found that 652 gene families were unique to DNS-1 and they were shaped from an ancestor. There were 1000 and 5193 gene families that expanded and contracted in the DNS-1 genome. The Rubus idaeus L. genome can be used to understand the structure and evolution of Rosaceae genomes and can be developed to identify genes controlling important traits and improve breeding work.

Circular RNA (circRNA) serves as a competitive endogenous RNA (ceRNA) that plays a pivotal role in the initiation and progression of breast cancer (BC). However, compared to other noncoding RNAs (ncRNAs), research on circRNA in BC is still in its infancy. Through the analysis of circRNA datasets in the GEO database, hsa_circ_0001314, which is upregulated in BC, was selected as the focus of this study. RT-qPCR analysis showed that hsa_circ_0001314 was significantly upregulated in BC tissues and cells. Subsequently, the biological functions of hsa_circ_0001314 in BC cells were examined through CCK-8, wound healing, transwell invasion, and flow cytometry analyses. The research demonstrated that knocking down the expression level of hsa_circ_0001314 significantly inhibited cell proliferation, migration, and invasion abilities while notably promoting cell apoptosis. Bioinformatics methods were used to predict downstream miRNAs and mRNAs that may interact with hsa_circ_0001314, constructing a ceRNA regulatory network related to hsa_circ_0001314. RT-qPCR confirmed that hsa_circ_0001314 functions as a sponge for hsa-miR-548aj-3p, competitively binding to hsa-miR-548aj-3p to activate the MAPK signaling pathway and regulate the expression of MAPK8 and MAP3K1. The findings uncover the potential of hsa_circ_0001314 as a novel prognostic biomarker and therapeutic target for BC patients.

Purpose: DNA primase subunit 2 (PRIM2) is a component of the DNA polymerase α-primase complex involved in DNA replication. Previous studies have implicated PRIM2 in cancer progression, but a comprehensive pan-cancer analysis is lacking. Here, we systematically analyzed PRIM2 across various cancer types to elucidate its potential role in cancer biology.

Methods: The expression data of PRIM2 was obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) databases. A range of bioinformatics tools were employed to analyze the expression of PRIM2 with the correlation of clinical data, diagnosis, prognosis, subtypes, immunomodulatory, and drug sensitivity. Further validation experiments were performed in HT-29 and HepG2 cell lines.

Results: PRIM2 expression was elevated in most tumor tissues, indicating its potential diagnostic value. Elevated PRIM2 levels affected prognosis and survival and varied with clinical status. Mutations and methylation events drove the aberrant expression of PRIM2 in various cancers. Furthermore, PRIM2 was linked to key immunoregulatory genes such as PD-L1 and infiltration of Th2 cells in tumor tissues. Our findings suggested that PRIM2 is correlated to immunotherapy and may be sensitive to specific small molecule PLK1 inhibitors. Knocking down PRIM2 in HT-29 and HepG2 cell lines reduced their proliferation, migration, invasion, and epithelial-mesenchymal transition.

Conclusion: This research highlights the potential of PRIM2 as a biomarker for cancer diagnosis and prognosis, and as a target for immunomodulatory therapy, offering valuable insights for clinical applications.

Identifying genetic regions and candidate genes that influence milk production traits is critical for understanding genetic inheritance and improving both the quality and quantity of milk in dairy cattle. Crossbred dairy cattle significantly contribute to increasing milk production and ensuring food security in the middle- and high-altitude regions of Ethiopia. However, the genetic architecture underlying their milk yield and composition traits has not yet been thoroughly investigated. This study conducted a genome-wide association study (GWAS) on 308 crossbred dairy cows from central, northeastern, and southern Ethiopia to identify genetic markers associated with key milk production traits. Using high-density SNP chip data and the fixed and random model circulating probability unification (Farm CPU) method via the Memory-efficient, Visualization-enhanced, and Parallel-accelerated R package (rMVP) (Version 1.0.7.), we analyzed traits including test-day milk yield (TDMY), total protein (TP), casein (CN), whey (W), protein percentage (P), fat percentage (F), lactose percentage (L), total solids (TS), density (D), solids-not-fat (SNF), salt (S), and freezing point (FP). This study identified 16 significant SNPs associated with these traits, including rs41661899 on Chromosome 6, which was significantly associated with both TP and W, and rs42274954 on Chromosome 12, which was significantly associated with CN. Eight SNPs, such as rs43560693, rs109098713, rs111029661, rs134499665, rs133908307, rs133627532, rs42098411, and rs110066280, were found across multiple chromosomes (8, 10, 14, 15, 19, 21, 26, and 28, respectively) and were significantly associated with milk P. Additionally, SNPs rs110844447 and rs135995768 on Chromosomes 6 and 14 were significantly associated with D and FP, respectively. Three SNPs, including rs109564259, rs135552551, and rs41620904 on Chromosomes 6, 11, and 24, were significant associations with S. Candidate genes identified near and within these SNPs include TRAM1L1, DIAPH3, PEBP4, WDR89, BCAS3, RALGAPA1, HABP2, NRG3, HPSE, PCDH7, LINC02579, TRNAS-GGA, and OR5CN1P. These findings enhance our understanding of the genetic architecture of milk-related traits in Ethiopian dairy cattle and highlight the potential for marker-assisted selection to improve milk production and composition in breeding programs.

Background: Neuroblastoma (NB) is one of the most devastating malignancies in children, accounting for a high mortality rate due to limited treatment options. This study is aimed at elucidating the role of the ferroptosis-related EIF2S1 gene in NB pathogenesis and exploring its potential as a therapeutic target.

Methods: We conducted comprehensive bioinformatics analyses utilizing the FerrDb database and NB-related transcriptomics data to investigate the role of EIF2S1 in NB. Changes in EIF2S1 expression were subsequently validated in NB tissues and cell lines. Loss-of-function experiments were performed in SK-N-SH and IMR-32 cell lines through shRNA-mediated EIF2S1 knockdown. The impact of EIF2S1 knockdown on the tumorigenesis of SK-N-SH cells was assessed in nude mice.

Results: Bioinformatics analyses revealed a significant association between elevated EIF2S1 expression and poor prognosis in NB patients. The increased levels of EIF2S1 expression were confirmed in NB tissues and cancerous cell lines. Furthermore, EIF2S1 overexpression was linked to translational regulation and immune cell infiltration modulation. Silencing of EIF2S1 resulted in the suppression of cell proliferation, migration, and tumorigenicity in NB cells. Additionally, EIF2S1 knockdown led to an accumulation of iron and oxidative stress, as well as a reduction in GPX4 and SLC7A11 expression.

Conclusion: Our findings indicate that EIF2S1 appears to facilitate the progression of NB by protecting tumor cells from ferroptosis through modulating GPX4 and SLC7A11 expression. Consequently, EIF2S1 may serve as a potential therapeutic target for the management of NB.

LncRNA is a major factor in the occurrence and development of many diseases. However, its mechanism in cerebral ischemia/reperfusion injury (CIRI) is yet unknown. In this study, the transcriptional level and methylation modification level of LncRNAs before and after mechanical thrombectomy were compared by high-throughput sequencing. Venn diagram, Spearman correlation analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, TargetScan, and miRanda were used to analyze the experimental data. The results showed that four key LncRNAs changed at both transcription and methylation levels. Specifically, LncRNA FAR2, LINC02431, and AL357060.1 were downregulated and hypomethylated, while LncRNA FOXD2-AS1 was upregulated and hypomethylated. Moreover, positive regulation of angiogenesis, protein domain–specific binding, autophagy pathway, PPAR signaling pathway, and MAPK signaling pathway were co-enriched between LncRNAs with different expression levels and different methylation levels. Finally, a LncRNA-miRNA-mRNA network was constructed. Therefore, this study explored the potential key LncRNAs and regulatory mechanisms of CIRI.

This study investigates the prognostic significance of SH3 and multiple ankyrin repeat domains 2 (SHANK2) gene expression in glioma patients, using data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, and the Gene Expression Omnibus (GEO). Through comprehensive analysis, we found a significant association between higher SHANK2 expression and improved survival outcomes across various glioma subtypes. To further validate the clinical relevance of SHANK2, we conducted cellular experiments involving siRNA-mediated knockdown of SHANK2 in U87 and A172 glioma cell lines. Quantitative real-time PCR (qPCR) and Western blot analyses confirmed the successful knockdown of SHANK2, and subsequent MTT assays revealed that silencing SHANK2 significantly promoted glioma cell proliferation. These findings underscore the potential role of SHANK2 as a tumor suppressor in glioma. The study also introduces a multivariate prognostic model incorporating SHANK2, providing a novel perspective on glioma prognosis. While the retrospective nature of the study presents limitations, our results suggest that SHANK2 expression could serve as a valuable biomarker for glioma prognosis and inform future therapeutic strategies.

Background: The influences of depression on cancer have noticeably attracted scholars’ attention. This study is aimed at exploring the relationships between depression and colon adenocarcinoma (COAD).

Methods: Differentially expressed genes in COAD were overlapped with depression-related genes (DRGs) to obtain COAD-DRGs. A risk model was constructed to predict overall survival (OS) using univariate and multivariate Cox regression analyses. GSE39582 dataset was utilized to validate the model. A nomogram was developed utilizing the clinical data.

Results: A risk model containing 11 genes was constructed. The results of receiver operating characteristic curve analysis revealed that the model could well predict the OS. In the high-risk group, the infiltration levels of plasma cells, resting/activated memory CD4 T cells, and monocytes were reduced, and only the infiltration levels of CD8 T cells and regulatory T cells were elevated. Cox regression analysis indicated that the risk score emerged as an independent prognostic factor. Finally, a nomogram of comprehensive risk score, age, and pM stage was established, and the predictions of this model aligned well with the actual OS data.

Conclusion: A COAD risk prediction model was successfully constructed utilizing 11 DRGs. This model assists in implementing more effective treatment and care strategies, enhancing the clinical outcomes for COAD.