Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal cell carcinoma (RCC), which is one of the most diagnosed urological malignancies worldwide, is usually associated with abnormality in both genetic and cellular processes. In the present study, through analyzing The Cancer Genome Atlas (TCGA) dataset, we screened out ERCC6L as a candidate gene that is potentially related to the development of RCC based on its increased expression in ccRCC tissues compared with normal kidney tissues as well as its possible relevance to cancer prognosis. Evidence indicates that ERCC6L is an indispensable component of mammalian cell mitosis, while it fails to disclose the role of ERCC6L in tumorigenesis. By using RT-PCR, it was confirmed that the mRNA expression of ERCC6L was upregulated in RCC tissues as compared to normal controls in 28 pared samples. In addition, the immunohistochemistry study in a tissue microarray (TMA) containing 150 ccRCC samples showed that the staining score of ERCC6L was positively correlated with the Fuhrman grade of cancers. Next, when the expression of ERCC6L was lowered by specific shRNA, the cell viability was significantly inhibited in 786-O and Caki-1 cells, while the apoptosis was induced accordingly. At the same time, RCC cells those were transfected with shRNA targeting to ERCC6L grew significantly slower than parental cells in immunodeficient mice. These results consistently suggest that ERCC6L may play a role in regulating the cell viability of RCC both in vitro and in vivo. Further, gene expression microarray analysis followed by the validating western blot after knocking down ERCC6L expression in 786-O cells highlighted the involvement of MAPK signaling pathway in regulation of ERCC6L on cellular process of RCC. In conclusion, the present study suggests a likely promoting role of ERCC6L on the development of RCC. Thus, further study to explore the potential utility of ERCC6L as a novel therapeutic target of RCC is clearly needed.
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PMID:ERCC6L that is up-regulated in high grade of renal cell carcinoma enhances cell viability in vitro and promotes tumor growth in vivo potentially through modulating MAPK signalling pathway. 3045 98

Background: Over the years, many efforts have been made to use the gene expression profiles of cancer types/subtypes to identify the prognostic genes with their potential clinical applications. However, one major challenge remains is to predict the common prognostic genes using simultaneously the dataset of multiple cancers, especially by considering the differences in survival, expression and the associated mutated pathways. Methods: Herein, we carried out a comprehensive examination for the prognostic genes and linked them to the mutational status of 29 cancers, so as to find independent prognostic genes and mechanisms. Additionally, their diagnostic value of them was also assessed. Results: our extensive analysis revealed: 1) the number of prognostic and diagnostic genes differs greatly across the cancers, 2) the potentially implicated 22 genes harbor the diagnostic as well as prognostic capacity, 3) the universal prognostic genes (CDC20, CDCA8, ASPM, ERCC6L, and GTSE1) were found to be involved in the spindle assembly checkpoint, 4) the prognostic genes were found to be statistically linked to the frequently mutated TP53-, MAPK-, PI3K- and AKT- related pathways. We also manually mined possible biological mechanisms for some of the statistical links in literatures. Conclusions: Taken together, we identified the prognostic genes and in addition we assessed their diagnostic capacity. Our analysis provides an important insight about the considerable overlapping between gene expression variation and the further associated altered mutational pathways across the cancer genome. We thus hypothesized that cancer related (mutated) genes are tightly connected and are capable to reshape the genome in multiple cancer types.
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PMID:Prognostic gene expression signature revealed the involvement of mutational pathways in cancer genome. 3248 68