Comparative and Functional Genomics最新文献

Background. Several studies have been conducted to investigate the role of cell division cycle-associated 5 (CDCA5) in cancer. Its role in breast cancer, however, remains unknown. Methods. The Gene Expression Omnibus and Cancer Genome Atlas Program databases provided the open-access information needed for the research. The CCK8 and colony formation assays were used to measure cell proliferation. The capacity of breast cancer cells to invade and migrate was assessed using the transwell assay. Results. In our study, CDCA5 was identified as the interested gene through a series of bioinformatics analysis. We found a higher CDCA5 expression level in tissue and cells of breast cancer. Meanwhile, CDCA5 has been linked to increased proliferation, invasion, and migration of breast cancer cells, which was also associated with worse clinical features. The biochemical pathways, in which CDCA5 was engaged, were identified using biological enrichment analysis. Immune infiltration research revealed that CDCA5 was linked to enhanced activity of several immune function terms. Meanwhile, DNA methylation might be responsible for the aberrant level of CDCA5 in tumor tissue. In addition, CDCA5 could significantly increase the paclitaxel and docetaxel sensitivity, indicating that it has the potential for clinical application. Also, we found that CDCA5 is mainly localized in cell nucleoplasm. Moreover, in the breast cancer microenvironment, we found that CDCA5 is mainly expressed in malignant cells, proliferation T cells, and neutrophils. Conclusion. Overall, our findings suggest that CDCA5 is a potential prognostic indicator and target for breast cancer, which can indicate the direction of the relevant research.

Background. Post-renal transplant patients have a high likelihood of developing renal cancer. However, the underlying biological mechanisms behind the development of renal cancer in post-kidney transplant patients remain to be elucidated. Therefore, this study aimed to investigate the underlying biological mechanism behind the development of renal cell carcinoma in post-renal transplant patients. Methods. Next-generation sequencing data and corresponding clinical information of patients with clear cell renal cell carcinoma (ccRCC) were obtained from The Cancer Genome Atlas Program (TCGA) database. The microarray data of kidney transplant patients with or without rejection response was obtained from the Gene Expression Omnibus (GEO) database. In addition, statistical analysis was conducted in R software. Results. We identified 55 upregulated genes in the transplant patients with rejection from the GEO datasets (GSE48581, GSE36059, and GSE98320). Furthermore, we conducted bioinformatics analyses, which showed that all of these genes were upregulated in ccRCC tissue. Moreover, a prognosis model was constructed based on four rejection-related genes, including PLAC8, CSTA, AIM2, and LYZ. The prognosis model showed excellent performance in prognosis prediction in a ccRCC cohort. In addition, the machine learning algorithms identified 19 rejection-related genes, including PLAC8, involved in ccRCC occurrence. Finally, the PLAC8 was selected for further research, including its clinical and biological role. Conclusion. In all, our study provides novel insight into the transition from the rejection of renal transplant to renal cancer. Meanwhile, PLAC8 could be a potential biomarker for ccRCC diagnosis and prognosis in post-kidney transplant patients.

Tomato chlorosis virus (ToCV), transmitted by the whitefly, Bemisia tabaci (Gennadius; Hemiptera: Aleyrodidae) has been continuously emerging on tomato plants and causing a significant economic loss throughout China. In the current study, RNA-Seq analysis was used to explore the gene expression profiles of B. tabaci Mediterranean (MED) that fed on both ToCV-infected and -uninfected tomato plants for 6, 12, 24, and 48 hours, respectively. The results revealed that dynamic changes occurred in the gene expressions of whiteflies at different time intervals after they acquired the virus. A total of 1709, 461, 4548, and 1748 differentially expressed genes (DEGs) were identified after a 6, 12, 24, and 48 hours feeding interval for the viral acquisition, respectively. The least number of expressed genes appeared in whiteflies with the 12 hours feeding treatment, and the largest numbers of those found in those with 24 hours feeding treatment. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that B. tabaci MED responded to ToCV acquisition through altering its nerve system development, fertility, detoxification, glucose metabolism, and immune function before it lost its ability to transmit the virus. The number of DEGs, degree of differential gene expressions, expression level of the same gene, involved biological processes, and metabolic functions in whiteflies post the 12 hours feeding, and viral acquisition were different from those from other three feeding treatments, which could be a significant finding suggesting an effective control of B. tabaci MED should be done less than 12 hours after whiteflies started feeding on ToCV-infected tomatoes. Our results further provided a clarified understanding in how B. tabaci was protected from viral acquisitions through comparison of the differential profile of gene expressions in whiteflies feeding on plants that were infected by semipersistent viruses.

Aim. We sought to profile gut microbiota’s role in combination of Bu Fei Hua Yu (BFHY) with cisplatin treatment. Methods. Non-small cell lung cancer (NSCLC) mice model were constructed followed by treatment with cisplatin alone or combined with BFHY. Mice weight and tumor volume were measured during the experiment. And mice cecum were detected by hematoxylin and eosin, cecum contents were collected for Enzyme Linked ImmuneSorbent Assay, and stool were profiled for metagenomic sequencing. Results. Combination of BFHY with cisplatin treatment decreased the tumor growth and relieved the damage of cecum. Expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β), monocyte chemotactic protein 1 (MCP), and interferon-γ (IFN-γ) were decreased compared with cisplatin treatment alone. Linear discriminant analysis effect size analysis showed that g_Parabacteroides was downregulated and g_Escherichia and g_Blautia were upregulated after cisplatin treatment. After combination with BFHY, g_Bacteroides and g_Helicobacter were decreased. g_Klebsiella, g_Unclssified_Proteobacteria, and g_Unclssified_Clostridiates were increased. Moreover, heatmap results showed that Bacteroides abundance was increased significantly after cisplatin treatment; BFHY combination treatment reversed this state. Function analysis revealed that multiple functions were slightly decreased in cisplatin treatment alone and increased significantly after combination with BFHY. Conclusion. Our study provided evidence of an efficacy of combination of BFHY with cisplatin on treatment of NSCLC and revealed that gut microbiota plays a role in it. The above results provide new ideas on NSCLC treatment.

Mesenchymal–epithelial transition (MET) factor is a proto-oncogene encoding tyrosine kinase receptor with hepatocyte growth factor (HGF) or scatter factor (SF). It is found on the human chromosome number 7 and regulates the diverse cellular mechanisms of the human body. The impact of mutations occurring in the MET gene is demonstrated by their detrimental effects on normal cellular functions. These mutations can change the structure and function of MET leading to different diseases such as lung cancer, neck cancer, colorectal cancer, and many other complex syndromes. Hence, the current study focused on finding deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) and their subsequent impact on the protein’s structure and functions, which may contribute to the emergence of cancers. These nsSNPs were first identified utilizing computational tools like SIFT, PROVEAN, PANTHER-PSEP, PolyPhen-2, I-Mutant 2.0, and MUpro. A total of 45359 SNPs of MET gene were accumulated from the database of dbSNP, and among them, 1306 SNPs were identified as non-synonymous or missense variants. Out of all 1306 nsSNPs, 18 were found to be the most deleterious. Moreover, these nsSNPs exhibited substantial effects on structure, binding affinity with ligand, phylogenetic conservation, secondary structure, and post-translational modification sites of MET, which were evaluated using MutPred2, RaptorX, ConSurf, PSIPRED, and MusiteDeep, respectively. Also, these deleterious nsSNPs were accompanied by changes in properties of MET like residue charge, size, and hydrophobicity. These findings along with the docking results are indicating the potency of the identified SNPs to alter the structure and function of the protein, which may lead to the development of cancers. Nonetheless, Genome-wide association study (GWAS) studies and experimental research are required to confirm the analysis of these nsSNPs.

Bovine respiratory disease (BRD) is one of the major health issues in the cattle industry, resulting in significant financial crises globally. There is currently no good treatment, and cattle are made resistant to pneumonia through disease-resistant breeding. The serial blood samples from six Xinjiang brown (XJB) calves were collected for the RNA sequencing (RNA-seq). The obtained six samples were grouped into two groups, in each group as infected with BRD and healthy calves, respectively. In our study, the differential expression mRNAs were detected by using RNA-seq and constructed a protein–protein interaction (PPI) network related to the immunity in cattle. The key genes were identified by protein interaction network analysis, and the results from RNA-seq were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 488 differentially expressed (DE) mRNAs were identified. Importantly, the enrichment analysis of these identified DEGs classified them as mainly enriched in the regulation and immune response processes. The 16 hub genes were found to be related to immune pathways categorized by PPIs analysis. Results revealed that many hub genes were related to the immune response to respiratory disease. These results will provide the basis for a better understanding of the molecular mechanism of bovine resistance to BRD.

Background. The genetic factors and pathogenesis of idiopathic dilated cardiomyopathy-induced heart failure (IDCM-HF) have not been understood thoroughly; there is a lack of specific diagnostic markers and treatment methods for the disease. Hence, we aimed to identify the mechanisms of action at the molecular level and potential molecular markers for this disease. Methods. Gene expression profiles of IDCM-HF and non-heart failure (NF) specimens were acquired from the database of Gene Expression Omnibus (GEO). We then identified the differentially expressed genes (DEGs) and analyzed their functions and related pathways by using “Metascape”. Weighted gene co-expression network analysis (WGCNA) was utilized to search for key module genes. Candidate genes were identified by intersecting the key module genes identified via WGCNA with DEGs and further screened via the support vector machine-recursive feature elimination (SVM-RFE) method and the least absolute shrinkage and selection operator (LASSO) algorithm. At last, the biomarkers were validated and evaluated the diagnostic efficacy by the area under curve (AUC) value and further confirmed the differential expression in the IDCM-HF and NF groups using an external database. Results. We detected 490 genes exhibiting differential expression between IDCM-HF and NF specimens from the GSE57338 dataset, with most of them being concentrated in the extracellular matrix (ECM) of cells related to biological processes and pathways. After screening, 13 candidate genes were identified. Aquaporin 3 (AQP3) and cytochrome P450 2J2 (CYP2J2) showed high diagnostic efficacy in the GSE57338 and GSE6406 datasets, respectively. In comparison to the NF group, AQP3 was significantly down-regulated in the IDCM-HF group, while CYP2J2 was significantly up-regulated. Conclusion. As far as we know, this is the first study that combines WGCNA and machine learning algorithms to screen for potential biomarkers of IDCM-HF. Our findings suggest that AQP3 and CYP2J2 could be used as novel diagnostic markers and treatment targets of IDCM-HF.

Vascular smooth muscle cells (VSMCs) are critical elements of the vascular wall and play a crucial role in the genesis and development of atherosclerosis (AS). Increasingly, studies have indicated that long noncoding RNAs (lncRNAs) regulate VSMC proliferation, apoptosis, and other biological processes. Nevertheless, the role of lncRNA NFIA-AS1 (hereinafter referred to as NFIA-AS1) in VSMCs and AS remains unclear. Quantitative real-time PCR (qRT-PCR) was performed to analyze the messenger RNA (mRNA) levels of NFIA-AS1 and miR-125a-3p. CCK-8 and EdU staining were performed to detect VSMC proliferation. VSMC apoptosis was evaluated by flow cytometry. The expression of various proteins was detected using western blotting. The levels of inflammatory cytokines secreted by VSMCs were measured by enzyme linked immunosorbent assay (ELISA). The binding sites of NFIA-AS1 and miR-125a-3p, as well as miR-125a-3p and AKT1, were analyzed using bioinformatics methods and validated using a luciferase reporter assay. The function of NFIA-AS1/miR-125a-3p/AKT1 in VSMCs was clarified through loss- and gain-of-functional experiments. We confirmed that NFIA-AS1 was highly expressed in AS tissues and VSMCs induced by oxidized low-density lipoprotein (Ox-LDL). Knockdown of NFIA-AS1 restrained the exceptional growth of Ox-LDL-induced VSMCs, promoted their apoptosis, and decreased the secretion of inflammatory factors and expression of adhesion factors. In addition, NFIA-AS1 regulated the proliferation, apoptosis, and inflammatory response of VSMCs through the miR-125a-3p/AKT1 axis, suggesting that NFIA-AS1 may be a potential therapeutic target for AS.

Climate change has become a major source of concern, particularly in agriculture, because it has a significant impact on the production of economically important crops such as wheat, rice, and maize. In the present study, an attempt has been made to identify differentially expressed heat stress-responsive long non-coding RNAs (lncRNAs) in the wheat genome using publicly available wheat transcriptome data (24 SRAs) representing two conditions, namely, control and heat-stressed. A total of 10,965 lncRNAs have been identified and, among them, 153, 143, and 211 differentially expressed transcripts have been found under 0 DAT, 1 DAT, and 4 DAT heat-stress conditions, respectively. Target prediction analysis revealed that 4098 lncRNAs were targeted by 119 different miRNA responses to a plethora of environmental stresses, including heat stress. A total of 171 hub genes had 204 SSRs (simple sequence repeats), and a set of target sequences had SNP potential as well. Furthermore, gene ontology analysis revealed that the majority of the discovered lncRNAs are engaged in a variety of cellular and biological processes related to heat stress responses. Furthermore, the modeled three-dimensional (3D) structures of hub genes encoding proteins, which had an appropriate range of similarity with solved structures, provided information on their structural roles. The current study reveals many elements of gene expression regulation in wheat under heat stress, paving the way for the development of improved climate-resilient wheat cultivars.

This study searched for aging-related genes (ARGs) to predict the prognosis of patients with cervical cancer (CC). All data were obtained from Molecular Signatures Database, Cancer Genome Atlas, Gene Expression Integration, and Genotype Organization Expression. The R software was used to screen out the differentially expressed ARGs (DE-ARGs) between CC and normal tissues. A protein–protein interaction network was established by the DE-ARGs. The univariate and multivariate Cox regression analyses were conducted on the first extracted Molecular Complex Detection component, and a prognostic model was constructed. The prognostic model was further validated in the testing set and GSE44001 dataset. Prognosis was analyzed by Kaplan–Meier curves, and accuracy of the prognostic model was assessed by receiver operating characteristic area under the curve analysis. An independent prognostic analysis of risk score and some clinicopathological factors of CC was also performed. The copy-number variant (CNV) and single-nucleotide variant (SNV) of prognostic ARGs were analyzed by the BioPortal database. A clinical practical nomogram was established to predict individual survival probability. Finally, we carried out cell experiment to further verify the prognostic model. An eight-ARG prognostic signature for CC was constructed. High-risk CC patients had significantly shorter overall survival than low-risk patients. The receiver operating characteristic (ROC) curve validated the good performance of the signature in survival prediction. The Figo_stage and risk score served as independent prognostic factors. The eight ARGs mainly enriched in growth factor regulation and cell cycle pathway, and the deep deletion of FN1 was the most common CNV. An eight-ARG prognostic signature for CC was successfully constructed.