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.
estrogens, shRNA knockdown of ERb and ectopic expression of ERb could affect RCC cell proliferation, migration and invasion. TCGA database analysis showed that the increased ERb is associated with a worse survival for RCC patients. Mechanism analysis revealed that ERb can promote RCC cell invasion via increasing transforming growth factor b1 (TGF-b1)/SMAD3 signals, and interrupting TGF-b 1/SMAD3 signals with a TGFb R1 inhibitor can reverse/block ERb -increased RCC cell migration.CONCLUSIONS: ERb can promote RCC cell invasion via upregulating TGF-b1)/SMAD3 signals. Compared to Faslodex and PHTPP, tamoxifen is not an effective anti-estrogen for RCC treatment. Importantly, preclinical analyses using in vivo mouse models of RCC revealed that targeting of this newly identified ERb/TGF-b1/SMAD3 pathway with either the FDA-approved antiestrogen ICI182,780 (Faslodex) or a selective ERb antagonist PHTPP can significantly reduce RCC tumor growth and invasion, which may be suitable as the basis for novel therapies to more effectively suppress metastatic RCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.