International Journal of Genomics最新文献

Background: Coronary artery ectasia (CAE) is an easily recognized abnormality of coronary artery anatomy and morphology. However, its pathogenesis remains unclear.

Objectives: This study aimed to identify abnormal methylation-modified genes in patients with CAE, which could provide a research basis for CAE.

Methods: Peripheral venous blood samples from patients with CAE were collected for RNA sequencing to identify differentially expressed genes (DEGs), followed by functional enrichment. Then, the DNA methylation profile of CAE was downloaded from GSE87016 (HumanMethylation450 BeadChip data, involving 11 cases and 12 normal controls) to identify differentially methylated genes (DMGs). Finally, after taking interaction genes between DEGs and DMGs, abnormal methylation-modified genes were identified, followed by protein-protein interaction analysis and expression validation using reverse transcriptase polymerase chain reaction.

Results: A total of 152 DEGs and 4318 DMGs were obtained from RNA sequencing and the GSE87016 dataset, respectively. After taking interaction genes, 9 down-regulated DEGs due to hypermethylation and 11 up-regulated DEGs due to hypomethylation were identified in CAE. A total of 10 core abnormal methylation-modified genes were identified, including six down-regulated DEGs due to hypermethylation (netrin G1, ADAM metallopeptidase domain 12, immunoglobulin superfamily member 10, sarcoglycan dela, Dickkopf WNT signaling pathway inhibitor 3, and GATA binding protein 6), and four up-regulated DEGs due to hypomethylation (adrenomedullin, ubiquitin specific peptidase 18, lymphocyte antigen 6 family member E, and MX dynamin-like GTPase 1). Some signaling pathways were identified in patients with CAE, including cell adhesion molecule, O-glycan biosynthesis, and the renin-angiotensin system.

Conclusions: Abnormal methylation-modified DEGs involved in signaling pathways may be involved in CAE development.

Head and neck squamous cell carcinoma (HNSCC) has become a prevalent malignancy, and its incidence and mortality rate are increasing worldwide. Accumulating evidence has indicated that lipid metabolism-related genes (LMRGs) are involved in the occurrence and development of HNSCC. This study investigated the latent association of lipid metabolism with HNSCC and established a prognostic signature based on LMRGs. A prognostic risk model composed of eight differentially expressed LMRGs (PHYH, CYP4F8, INMT, ELOVL6, PLPP3, BCHE, TPTE, and STAR) was constructed through The Cancer Genome Atlas database. Then, ELOVL6 expression was validated in oral squamous cell carcinoma (OSCC), which is a common type of HNSCC, by immunohistochemical analysis. ELOVL6 expression in the OSCC II/III group was significantly higher than that in the other three groups (normal, dysplasia, and OSCC I), and OSCC patients with high ELOVL6 expression had poorer survival than those with low ELOVL6 expression. In summary, the LMRG-based prognostic feature had prognostic predictive capacity. ELOVL6 may be a potential prognostic factor for HNSCC patients.

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.

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.

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.

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.

Background: Recent studies indicate that circular RNAs (circRNAs) have been implicated in the initiation or progression of a wide spectrum of diseases. In the current study, we explored the potential engagement of circ_0008285 in glioma and investigated the downstream regulators.

Methods: The detection of circ_0008285 level in glioma specimens and cell lines was conducted by quantitative real-time polymerase chain reaction. The chi-squared test was employed to evaluate the relationship between the circ_0008285 level and the clinical features of glioma patients. The roles of circ_0008285 on the proliferation and apoptosis of glioma cells were studied by knockdown experiment. Meanwhile, the regulatory relationship of circ_0008285, miR-384, and high mobility group protein B1 (HMGB1) was explored in glioma cells, and we explored the effects of circ_0008285/miR-384/HMGB1 pathway on glioma cells.

Results: In glioma specimens and cell lines, the expression of circ_0008285 was significantly increased, and a high circ_0008285 level was associated with a larger tumor size and more advanced grading in glioma patients. Furthermore, downregulating circ_0008285 suppressed proliferation and triggered apoptosis of glioma cells, which was associated with a cell cycle arrest at the G1/G0 phase. Mechanism studies indicated that circ_0008285 regulated HMGB1 by sponging miR-384. Functional experiments demonstrated that circ_0008285 promoted the malignant phenotype of glioma cells by miR-384/HMGB1 axis.

Conclusion: Our study revealed circ_0008285 as a novel oncogenic factor in glioma through modulating the miR-384/HMGB1 pathway, suggesting that targeting circ_0008285 could serve as a strategy for glioma management.

Abnormal stratifin (SFN) expression is closely related to the progression of several human cancers, but the potential roles of SFN in hepatocellular carcinoma (HCC) remain largely unknown. In this study, we found that SFN was upregulated in HCC cell lines and tissues and was positively associated with tumor size, poor differentiation, Tumor Node Metastasis (TNM) stage, and vascular invasion. In addition, high expression levels of SFN were associated with poor overall survival and disease-free survival. Biologically, downregulation of SFN suppressed tumor cell proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration in vitro and tumor growth in vivo. However, overexpression of SFN promoted cell proliferation, EMT, invasion, and migration in vitro and tumor growth in vivo. Mechanistically, overexpression of SFN activated the Wnt/β-catenin pathway by promoting Glycogen synthase kinase-3 beta (GSK-3β) phosphorylation, decreasing β-catenin phosphorylation, promoting β-catenin transport into the nucleus, and enhancing the expression of c-Myc, whereas depletion of SFN inhibited the Wnt/β-catenin pathway. In addition, TOPFlash/FOPFlash reporter assays showed that overexpression or downregulation of SFN obviously increased or decreased, respectively, the activity of the Wnt/β-catenin pathway. Our results indicated that SFN plays an important role in HCC, possibly providing a prognostic factor and therapeutic target for HCC.

Background: Primary liver cancer, dominated by hepatocellular carcinoma (HCC), is one of the most common cancer types and the third leading cause of cancer death in 2020. Previous studies have shown that liquid-liquid phase separation (LLPS) plays an important role in the occurrence and development of cancer including HCC, but its influence on the patient prognosis is still unknown. It is necessary to explore the effect of LLPS genes on prognosis to accurately forecast the prognosis of HCC patients and identify relevant targeted therapeutic sites.

Methods: Using The Cancer Genome Atlas dataset and PhaSepDB dataset, we identified LLPS genes linked to the overall survival (OS) of HCC patients. We applied Least Absolute Shrinkage and Selection Operator (LASSO) Cox penalized regression analysis to choose the best genes for the risk score prognostic signature. We then analysed the validation dataset and evaluated the effectiveness of the risk score prognostic signature. Finally, we performed quantitative real-time PCR experiments to validate the genes in the prognostic signature.

Results: We identified 43 differentially expressed LLPS genes that were associated with the OS of HCC patients. Five of these genes (BMX, FYN, KPNA2, PFKFB4, and SPP1) were selected to generate a prognostic risk score signature. Patients in the low-risk group were associated with better OS than those in the high-risk group in both the training dataset and the validation dataset. We found that BMX and FYN had lower expression levels in HCC tumour tissues, whereas KPNA2, PFKFB4, and SPP1 had higher expression levels in HCC tumour tissues. The validation demonstrated that the five-LLPS gene risk score signature has the capability of predicting the OS of HCC patients.

Conclusion: Our study constructed a five-LLPS gene risk score signature that can be applied as an effective and convenient prognostic tool. These five genes might serve as potential targets for therapy and the treatment of HCC.