BackgroundProstate cancer (PCa) is one of the most common cancers in male worldwide. Oxidative stress has been recognized as one of the driving signals pathologically linked to PCa progression. Nevertheless, the association of oxidative stress with PCa progression remains unclear.MethodsWestern blot, q-RT-PCR and bioinformatics analyses were used to examine PAGE4 expression. Comet assay and Annexin V/ PI dual staining assay were performed to investigate DNA damage and cell death under oxidative stress. Mouse xenograft model of PCa cells was established to verify the role of PAGE4 in vivo. Transcriptomic analysis was performed to investigate the underlying mechanism for the function of PAGE4 under oxidative stress. Western blot assay was conducted to determine the status of MAPK pathway. Immunohistochemistry was used to identify protein expression of PAGE4 in tumor tissues.ResultsIn this study, we found that PAGE4 expression was increased in PCa cells under oxidative stress condition. PAGE4 overexpression protected PCa cells from oxidative stress-inducing cell death by reducing DNA damage. PAGE4 overexpression promoted PCa cells growth in vivo. Mechanistically, PAGE4 promoted the survival of prostate cancer cells through regulating MAPK pathway which reflected in decreasing the phosphorylation of MAP2K4, JNK and c-JUN but increasing phosphorylation of ERK1/2.ConclusionOur findings indicate that PAGE4 protects PCa cells from DNA damage and apoptosis under oxidative stress by modulating MAPK signalling pathway. PAGE4 expression may serve as a prognostic biomarker for clinical applications.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1032-3) contains supplementary material, which is available to authorized users.
Renal cell carcinoma (RCC) is the most common type of kidney cancer. By analysing The Cancer Genome Atlas (TCGA) database, 16 genes were identified to be consistently highly expressed in RCC tissues compared with the matched para-tumour tissues. Using a high-throughput cell viability screening method, it was found that downregulation of only two genes significantly inhibited the viability of 786-O cells. Among the two genes, pleckstrin homology domain containing O1 (PLEKHO1) has never been studied in RCC, to the best of our knowledge, and its expression level was shown to be associated with the prognosis of patients with RCC in TCGA dataset. The upregulation of PLEKHO1 in RCC was first confirmed in 30 paired tumour and para-tumour tissues. Then, the effect of PLEKHO1 on cell proliferation and apoptosis was assessed
in vitro
. Additionally, xenograft tumour models were established to investigate the function of PLEKHO1
in vivo
. The results showed that PLEKHO1 knockdown significantly inhibited cell viability and facilitated apoptosis
in vitro
and impaired tumour formation
in vivo
. Thus, PLEKHO1 is likely to be associated with the viability of RCC cells
in vitro
and
in vivo
. Further gene expression microarray and co-expression analyses showed that PLEKHO1 may be involved in the serine/threonine-protein kinase hippo and JNK signalling pathways. Together, the results of the present study suggest that PLEKHO1 may contribute to the development of RCC, and therefore, further study is needed to explore its potential as a therapeutic target.
RNA‑binding motif 3 (RBM3) is a cold‑shock protein that has been previously shown to attenuate cancer stem cell‑like features in prostate cancer (PCa) cells. However, the mechanism underlying RBM3 regulation in PCa cells is largely unknown. The present study investigated the impact of RBM3 expression on the whole transcriptome of PCa cells using high‑throughput RNA sequencing (RNA‑seq). Differentially expressed genes (DEGs) that were identified through RNA‑seq were applied to Gene Ontology (GO), pathway analysis, pathway‑action networks and protein‑protein interaction network analysis. GO and pathway ananlyses showed that RBM3 expression was associated with several metabolism pathways. Combining GO analysis and pathway analysis, certain DEGs, including phospholipase A2 group IIA (PLA2G2A), PLA2G2F, PLA2G4C, endothelin 1, cytochrome P450 family 2 subfamily B member 6, G protein subunit γ5, nitric oxide synthase 3 and CD38 molecule, were shown to be closely associated with RBM3 regulation in PCa cells. Furthermore, the changes in expression of selected genes upon RBM3‑knockdown in RNA‑seq were confirmed by separate reverse transcription‑quantitative‑polymerase chain reaction, validating the results of RNA‑seq. Thus, the present study provides a series of valuable reference genes and pathways for the future study of the pathogenic role of RBM3 in the development of PCa.
Abstract-Businesscorrespondence is a written communication in the trade between the two sides. During the exchanges of business correspondence, the view of the two sides is to be expressed and communicated as well as ideas and information. Therefore, an effective exchange of business correspondence can help domestic manufacturers and foreign customers establish or maintain a long-term friendly relationship. Undoubtedly, it is particularly important to learn how to write a successful business correspondence. However, just copying theoretical principles from the text is not enough. This paper takes "3C" principles, a standard of a good business correspondence generally accepted in academic field and British linguist G.N. Leech's famous politeness principles as a theoretical background, analyzing the characteristics of the language used in BC, respectively in terms of its lexical characteristic and its structural characteristics in sentences. Then, in order to batter grasp the key to write a successful business correspondence, some main writing principle like polite principle will be specifically analyzed.
Background: Multiple myeloma (MM) is a common plasma cell malignancy that is currently incurable. Finding potential drug targets and new drugs are crucial for the treatment of thisdisease. Microarray technology is widely used to investigate differential mRNA expression and identify biomarkers in disease, which provides important clues to identifying new treatment targets and then new drugs could be designed. Aims: To find new treatment target for MM and design targeting affinity peptide. Methods: Two datasets (GSE6691 and GSE39754) were obtained from the Gene Expression Omnibus (GEO) database, and a protein-protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed to identify hub genes.Key clusters in the PPI network were analyzed by Molecular Complex Detection (MCODE). The gene both in hub genes and key clusters could be considered as potential treatment target and will be verified in clinical patients' bone marrow samples. As the treatment target identified, crystal structure is obtained from Protein Data Bank and affinity peptide drug designed by Molecular Operating Environment (MOE) software. Results: HLA-E was identified as hub gene and also located in one of the key clusters which could be a potential therapeutic target for MM.The high expression of HLA-E in myeloma cells was confirmed by measuring HLA-E mRNA expression in bone marrow samples from MM patients and healthy volunteers from Shengjing Hospital.The crystal structure of HLA-E from the Protein Data Bank(PDB ID: 3CDG) was used to find the key active area of HLA-E. MOE softwarewas used to design high-affinity targeting peptides using key interaction amino acids as model peptides. A peptide library was constructed and screened to identify peptides with the highest stability and affinity for HLA-E. Three high-affinity peptides were selected and verified by peptide-protein docking. Thus, these peptides could serve as targeting heads to find myeloma cells that express high levels of HLA-E.
Summary/Conclusion:HLA-E could be recognized as a new treatment target for MM. At the meanwhile, affinity peptide(NALDEYCEDKNR) could be considered as a new targeting drug.
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