scholarly journals Identification of Key MicroRNAs and Mechanisms in Prostate Cancer Evolution Based on Biomarker Prioritization Model and Carcinogenic Survey

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuxin Lin ◽  
Zhijun Miao ◽  
Xuefeng Zhang ◽  
Xuedong Wei ◽  
Jianquan Hou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cancer Evolution ◽  
Network Systems ◽  
Holistic Management ◽  
Study Gene Expression ◽  
Association Data ◽  
Translational Informatics

Background: Prostate cancer (PCa) is occurred with increasing incidence and heterogeneous pathogenesis. Although clinical strategies are accumulated for PCa prevention, there is still a lack of sensitive biomarkers for the holistic management in PCa occurrence and progression. Based on systems biology and artificial intelligence, translational informatics provides new perspectives for PCa biomarker prioritization and carcinogenic survey.Methods: In this study, gene expression and miRNA-mRNA association data were integrated to construct conditional networks specific to PCa occurrence and progression, respectively. Based on network modeling, hub miRNAs with significantly strong single-line regulatory power were topologically identified and those shared by the condition-specific network systems were chosen as candidate biomarkers for computational validation and functional enrichment analysis.Results: Nine miRNAs, i.e., hsa-miR-1-3p, hsa-miR-125b-5p, hsa-miR-145-5p, hsa-miR-182-5p, hsa-miR-198, hsa-miR-22-3p, hsa-miR-24-3p, hsa-miR-34a-5p, and hsa-miR-499a-5p, were prioritized as key players for PCa management. Most of these miRNAs achieved high AUC values (AUC > 0.70) in differentiating different prostate samples. Among them, seven of the miRNAs have been previously reported as PCa biomarkers, which indicated the performance of the proposed model. The remaining hsa-miR-22-3p and hsa-miR-499a-5p could serve as novel candidates for PCa predicting and monitoring. In particular, key miRNA-mRNA regulations were extracted for pathogenetic understanding. Here hsa-miR-145-5p was selected as the case and hsa-miR-145-5p/NDRG2/AR and hsa-miR-145-5p/KLF5/AR axis were found to be putative mechanisms during PCa evolution. In addition, Wnt signaling, prostate cancer, microRNAs in cancer etc. were significantly enriched by the identified miRNAs-mRNAs, demonstrating the functional role of the identified miRNAs in PCa genesis.Conclusion: Biomarker miRNAs together with the associated miRNA-mRNA relations were computationally identified and analyzed for PCa management and carcinogenic deciphering. Further experimental and clinical validations using low-throughput techniques and human samples are expected for future translational studies.

scholarly journals Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yu Sun ◽  
Sheng-Hua Li ◽  
Ji-Wen Cheng ◽  
Gang Chen ◽  
Zhi-Guang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Protein Level ◽  
Target Genes ◽  
Mrna Level ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Forest Plot ◽  
Biological Mechanism

Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.

Integrative Analysis of four miRNA prognostic signatures of prostate cancer

2020 ◽  
Author(s):  
Chen Chi ◽  
Xianwu Chen ◽  
Liping Yao ◽  
Min Li ◽  
Lanting Xiang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Relationship Of

Abstract Background Prostate cancer (PCa) is the most common urological cancer among men, having a poor prognosis, which is hard to accurately evaluate based on the present methods. MicroRNAs (miRNAs), a class of internal non-coding small RNA, can involve in the regulation of tumor biological function. So far, many researchers have tried to explore the relationship of malignant progress of PCa with miRNA, while there are just limited studies conducting the comprehensive analysis of miRNA in PCa clinical significance. Methods The data of miRNA and mRNA expressions in PCa were downloaded from TCGA database, and were performed the overall survival (OS) analysis using Survival package of R software to harvest the differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs). The bioinformatics tools such as TargetScan, miRDB, and miRanda were also conducted to forecast the desired target genes related with prognostic DEMs. In addition, both GO and KEGG analyses were used to uncover the fundamental signaling pathways and cellular processes in PCa as well as the protein-protein interaction (PPI) network was constructed through STRING and Cytoscape software. Results Firstly, 4 DEMs (miR-19a-3p, miR-144-3p, miR-223-5p, and miR-483-3p) were found having significantly associated with overall survival in PCa. Based on the criteria with FDR < 0.05 and |log2FC| > 1, 33 genes were screened out as DEGs. Besides, the functional enrichment analysis revealed that these DEGs of 4 miRNAs may participate in cancer-related pathways like FoxO and PI3K-Akt signaling pathway. Lastly, the low expression of CD177 may be potentially associated with poor survival of patients in PCa. Conclusion This study systematically analyzed multiple PCa prognostic DEMs (miR-19a-3p, miR-144-3p, miR-223-5p, and miR-483-3p), and verified a novel DEG signature (CD177) that can be used to effectively assess the prognosis of PCa patients.

scholarly journals Comprehensive analysis of tumour mutational burden and its clinical significance in prostate cancer

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lijuan Wang ◽  
Shucheng Pan ◽  
Binbin Zhu ◽  
Zhenliang Yu ◽  
Wei Wang
Keyword(s):  
Prostate Cancer ◽  
Disease Free Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Comprehensive Analysis ◽  
Functional Enrichment ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Dna Mutation ◽  
Mutational Burden

Abstract Background The tumorigenesis of prostate cancer involves genetic mutations. Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immunotherapy. Results Single-nucleotide polymorphisms were the most common variant type, and C>T transversion was the most commonly presented type of single-nucleotide variant. The high-TMB group had lower overall survival (OS) than the low-TMB group. TMB was associated with age, T stage and N stage. Functional enrichment analysis of differentially expressed genes (DEGs) showed that they are involved in pathways related to the terms spindle, chromosomal region, nuclear division, chromosome segregation, cell cycle, oocyte meiosis and other terms associated with DNA mutation and cell proliferation. Six hub genes, PLK1, KIF2C, MELK, EXO1, CEP55 and CDK1, were identified. All the genes were associated with disease-free survival, and CEP55 and CDK1 were associated with OS. Conclusions The present study provides a comprehensive analysis of the significance of TMB and DEGs and infiltrating immune cells related to TMB, which provides helpful information for exploring the significance of TMB in prostate cancer.

Investigation of Key Genes associated with Prostate Cancer using RNA-Seq Data

2014 ◽  
Vol 29 (1) ◽  
pp. e86-e92 ◽  
Author(s):  
Jitao Wu ◽  
Fan Feng ◽  
Diandong Yang ◽  
Shengqiang Yu ◽  
Jianqiu Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Normal Sample ◽  
Pathway Enrichment Analysis ◽  
Rna Seq ◽  
Cancer Sample ◽  
Key Genes

We aimed to identify key genes associated with prostate cancer using RNA-sequencing (RNA-seq) data. RNA-seq data, including 1 cancer sample and 1 adjacent normal sample, were downloaded from the NCBI SRA database and the differentially expressed genes (DEGs) were identified with the software Cufflinks. Functional enrichment analysis was performed to uncover the biological functions of DEGs. Regulatory information was retrieved from the IPA database and a network was established. A total of 147 DEGs were obtained, including 96 downregulated and 51 upregulated DEGs. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that metabolism and signal transduction were the 2 major functions that were significantly influenced. Moreover, an interaction network was built. In conclusion, a number of DEGs was identified and their roles in the pathogenesis of cancer were supported by previous studies. More studies are necessary to further validate their usefulness in the diagnosis and treatment of prostate cancer.

Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

2019 ◽  
Vol 14 (7) ◽  
pp. 591-601 ◽  
Author(s):  
Aravind K. Konda ◽  
Parasappa R. Sabale ◽  
Khela R. Soren ◽  
Shanmugavadivel P. Subramaniam ◽  
Pallavi Singh ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Wrky Transcription Factor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Callose Deposition ◽  
Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

scholarly journals Structural variations in papaya genomes

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenyang Liao ◽  
Xunxiao Zhang ◽  
Shengcheng Zhang ◽  
Zhicong Lin ◽  
Xingtan Zhang ◽  
...  
Keyword(s):  
Agronomic Traits ◽  
Enrichment Analysis ◽  
Copy Number Variant ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Structural Variations ◽  
Reproduction Traits ◽  
Depth Study ◽  
Environmental Adaptability ◽  
The Impact

Abstract Background Structural variations (SVs) are a type of mutations that have not been widely detected in plant genomes and studies in animals have shown their role in the process of domestication. An in-depth study of SVs will help us to further understand the impact of SVs on the phenotype and environmental adaptability during papaya domestication and provide genomic resources for the development of molecular markers. Results We detected a total of 8083 SVs, including 5260 deletions, 552 tandem duplications and 2271 insertions with deletion being the predominant, indicating the universality of deletion in the evolution of papaya genome. The distribution of these SVs is non-random in each chromosome. A total of 1794 genes overlaps with SV, of which 1350 genes are expressed in at least one tissue. The weighted correlation network analysis (WGCNA) of these expressed genes reveals co-expression relationship between SVs-genes and different tissues, and functional enrichment analysis shows their role in biological growth and environmental responses. We also identified some domesticated SVs genes related to environmental adaptability, sexual reproduction, and important agronomic traits during the domestication of papaya. Analysis of artificially selected copy number variant genes (CNV-genes) also revealed genes associated with plant growth and environmental stress. Conclusions SVs played an indispensable role in the process of papaya domestication, especially in the reproduction traits of hermaphrodite plants. The detection of genome-wide SVs and CNV-genes between cultivated gynodioecious populations and wild dioecious populations provides a reference for further understanding of the evolution process from male to hermaphrodite in papaya.

scholarly journals CCTs as new biomarkers for the prognosis of head and neck squamous cancer

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 672-688
Author(s):  
Yanbo Dong ◽  
Siyu Lu ◽  
Zhenxiao Wang ◽  
Liangfa Liu
Keyword(s):  
Head And Neck ◽  
Survival Data ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Advanced Tumor Stage ◽  
Expression Levels ◽  
T Complex ◽  
Advanced Tumor ◽  
Squamous Cancer

AbstractThe chaperonin-containing T-complex protein 1 (CCT) subunits participate in diverse diseases. However, little is known about their expression and prognostic values in human head and neck squamous cancer (HNSC). This article aims to evaluate the effects of CCT subunits regarding their prognostic values for HNSC. We mined the transcriptional and survival data of CCTs in HNSC patients from online databases. A protein–protein interaction network was constructed and a functional enrichment analysis of target genes was performed. We observed that the mRNA expression levels of CCT1/2/3/4/5/6/7/8 were higher in HNSC tissues than in normal tissues. Survival analysis revealed that the high mRNA transcriptional levels of CCT3/4/5/6/7/8 were associated with a low overall survival. The expression levels of CCT4/7 were correlated with advanced tumor stage. And the overexpression of CCT4 was associated with higher N stage of patients. Validation of CCTs’ differential expression and prognostic values was achieved by the Human Protein Atlas and GEO datasets. Mechanistic exploration of CCT subunits by the functional enrichment analysis suggests that these genes may influence the HNSC prognosis by regulating PI3K-Akt and other pathways. This study implies that CCT3/4/6/7/8 are promising biomarkers for the prognosis of HNSC.

scholarly journals Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

2021 ◽  
Vol 28 (1) ◽  
pp. 20-33
Author(s):  
Lydia-Eirini Giannakou ◽  
Athanasios-Stefanos Giannopoulos ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
Erasmia Rouka ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Respiratory Pathogens ◽  
Gram Negative ◽  
Human Proteins ◽  
Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

scholarly journals Isolation and identification of a novel bacterium, Pseudomonas sp. ZyL-01, involved in the biodegradation of CL-20

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhiyong Liu ◽  
Kai Dang ◽  
Cunzhi Li ◽  
Junhong Gao ◽  
Hong Wang ◽  
...  
Keyword(s):  
Microbial Community ◽  
Environmental Fate ◽  
Draft Genome ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Community Diversity ◽  
Functional Enrichment ◽  
Metagenomic Sequencing ◽  
Isolation And Identification ◽  
Novel Bacterium

Abstract Hexanitrohexaazaisowurtzitane (CL-20) is a compound with a polycyclic cage and an N-nitro group that has been shown to play an unfavorable role in environmental fate, biosafety, and physical health. The aim of this study was to isolate the microbial community and to identify a single microbial strain that can degrade CL-20 with desirable efficiency. Metagenomic sequencing methods were performed to investigate the dynamic changes in the composition of the community diversity. The most varied genus among the microbial community was Pseudomonas, which increased from 1.46% to 44.63% during the period of incubation (MC0–MC4). Furthermore, the new strain was isolated and identified from the activated sludge by bacterial morphological and 16s rRNA sequencing analyses. The CL-20 concentrations decreased by 75.21 μg/mL and 74.02 μg/mL in 48 h by MC4 and Pseudomonas sp. ZyL-01, respectively. Moreover, ZyL-01 could decompose 98% CL-20 of the real effluent in 14 day’s incubation with the glucose as carbon source. Finally, a draft genome sequence was obtained to predict possible degrading enzymes involved in the biodegradation of CL-20. Specifically, 330 genes that are involved in energy production and conversion were annotated by Gene Ontology functional enrichment analysis, and some of these candidates may encode enzymes that are responsible for CL-20 degradation. In summary, our studies indicate that microbes might be a valuable biological resource for the treatment of environmental contamination caused by CL-20 and that Pseudomonas sp. ZyL-01 might be a promising candidate for eradicating CL-20 to achieve a more biosafe environment and improve public health.

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