ABSTRACT
Early-onset breast cancer is the most prevalent cancer in the female. To identify the differentially expressed genes and the key signaling pathways in early-onset breast cancer, we have carried out the bioinformatic analysis of an RNA array dataset in the GEO database, GSE109169, which was acquired from early-onset breast cancer patient. A total of 118 differentially expressed genes in early-onset breast cancer were significantly changed compared with that in adjacent normal tissues. Most of these genes are classified into three categories: signaling molecule, enzyme modulator, and hydrolase. Gene ontology terms reveal that most of these genes are involved in cellular and metabolic processes, biological regulation, binding and catalytic activities, and receptor regulation. Protein-protein interaction network was constructed and has two highly enriched modules: one with up-regulated genes and the other with down-regulated genes. The singling pathways are mainly enriched in the cellular immune system, lipid metabolism and other types of metabolic pathways. Finally, we have plotted the Kaplan-Meier curves of two up-regulated and two down-regulated genes for the overall survival prediction in breast cancer. These results greatly expand the current view of early-onset breast cancer and shed light on the discovery of drug candidates and the improvement for the prognosis.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Adult , Age Factors , Breast Neoplasms/mortality , Computational Biology , Databases, Genetic , Female , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic , Gene Ontology , Humans , Kaplan-Meier Estimate , Oligonucleotide Array Sequence Analysis/methods , Protein Interaction Mapping , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Signal TransductionABSTRACT
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. However, the exact pathophysiology of PCOS remains largely unclear. We performed deep sequencing to investigate the mRNA and long noncoding RNA (lncRNA) expression profiles in the ovarian tissues of letrozole-induced PCOS rat model and control rats. A total of 2147 mRNAs and 158 lncRNAs were differentially expressed between the PCOS models and control. Gene ontology analysis indicated that differentially expressed mRNAs were associated with biological adhesion, reproduction, and metabolic process. Pathway analysis results indicated that these aberrantly expressed mRNAs were related to several specific signaling pathways, including insulin resistance, steroid hormone biosynthesis, PPAR signaling pathway, cell adhesion molecules, autoimmune thyroid disease, and AMPK signaling pathway. The relative expression levels of mRNAs and lncRNAs were validated through qRT-PCR. LncRNA-miRNA-mRNA network was constructed to explore ceRNAs involved in the PCOS model and were also verified by qRTPCR experiment. These findings may provide insight into the pathogenesis of PCOS and clues to find key diagnostic and therapeutic roles of lncRNA in PCOS.
Subject(s)
Gene Expression Profiling/methods , Nitriles/adverse effects , Ovary/chemistry , Polycystic Ovary Syndrome/genetics , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Triazoles/adverse effects , Animals , Disease Models, Animal , Female , Gene Expression Regulation , Gene Ontology , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing/methods , Humans , Letrozole , Polycystic Ovary Syndrome/chemically induced , Rats , Sequence Analysis, RNA/methodsABSTRACT
The differential expression of genes in HepG2 cells caused by UC001kfo RNAi was investigated using RNA-seq. HepG2 cells were infected by Lenti-shUC001kfo lentivirus particles. The expression of UC001kfo mRNA in the HepG2-shUC001kfo cell line was detected by real-time PCR. RNA-seq technology was used to identify the difference in the expression of genes regulated by lncRNA UC001kfo in the HepG2 cell line. Gene ontology and signaling pathway analysis were performed to reveal the biological functions of the genes encoding of significantly different mRNAs. The results showed that mRNAs were differentially expressed between the HepG2-shUC001kfo cell line and the HepG2 cell line. The UC001kfo mRNA was significantly down-regulated in the stable cell line HepG2-shUC001kfo (P<0.001). Additionally, we found 19 signaling pathways or functional classifications encompassing 30 genes that played a role in cancer characteristics, cell adhesion, invasion and migration. The results also showed that the expression of many genes associated with cancer cell invasion and metastasis was decreased with the down-regulation of the lncRNA UC001kfo. LncRNA UC001kfo may play a role in regulating cancer cell invasion and metastasis. It was suggested that mRNAs were differentially expressed in the HepG2 cell line after the down-regulation of lncRNA-UC001kfo. Some took part in the extracellular matrix, cell adhesion, motility, growth, and localization. The genes encoding of differentially expressed mRNAs may participate in cell invasion and metastasis.
Subject(s)
Gene Expression Regulation, Neoplastic , RNA Interference , RNA, Long Noncoding/genetics , Sequence Analysis, RNA , Down-Regulation/genetics , Gene Ontology , Hep G2 Cells , Humans , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction/geneticsABSTRACT
The differential expression of genes in HepG2 cells caused by UC001kfo RNAi was investigated using RNA-seq.HepG2 cells were infected by Lenti-shUC001kfo lentivirus particles.The expression of UC001kfo mRNA in the HepG2-shUC001kfo cell line was detected by real-time PCR.RNA-seq technology was used to identify the difference in the expression of genes regulated by lncRNA UC001kfo in the HepG2 cell line.Gene ontology and signaling pathway analysis were performed to reveal the biological functions of the genes encoding of significantly different mRNAs.The results showed that mRNAs were differentially expressed between the HepG2-shUC001kfo cell line and the HepG2 cell line.The UC001kfo mRNA was significantly down-regulated in the stable cell line HepG2-shUC001kfo (P＜0.001).Additionally,we found 19 signaling pathways or functional classifications encompassing 30 genes that played a role in cancer characteristics,cell adhesion,invasion and migration.The results also showed that the expression of many genes associated with cancer cell invasion and metastasis was decreased with the down-regulation of the lncRNA UC001kfo.LncRNA UC001kfo may play a role in regulating cancer cell invasion and metastasis.It was suggested that mRNAs were differentially expressed in the HepG2 cell line after the down-regulation of lncRNA-UC001kfo.Some took part in the extracellular matrix,cell adhesion,motility,growth,and localization.The genes encoding of differentially expressed mRNAs may participate in cell invasion and metastasis.
ABSTRACT
Isoproterenol, a ß-adrenergic agonist, has been shown to induce salivary gland hyperplasia. However, the mechanism involved in this pharmacological phenomenon is not well understood. To gain a better understanding of the underlying changes, including genes, networks and pathways altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 min after isoproterenol injection. After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. Pathway analysis showed that cell hyperplasia, p38(MAPK), and IGF-1 were the most altered function, network and pathway, respectively. The balanced regulation of up- and down-expression of genes related to cell proliferation/survival may provide a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement without tumor transformation.
