Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melanoma is a common and high-mortality skin cancer. Oxidative stress and DNA damage caused by ultraviolet light (UV) are major causative factors of melanoma formation. However, the specific molecular mechanism is still unclear. In this study, 218 dysregulated genes and 104 dysregulated miRNAs in response to UV were screened by analyzing sequencing datasets. Among them, 29 up-regulated miRNAs and 28 down-regulated miRNAs were involved in the melanoma pathway. As the only differential gene in the melanoma pathway, GADD45B severely affects the prognosis of melanoma patients. MiR-300 is the only differentially expressed miRNA that regulates GADD45B. In addition, compared to normal melanocytes, miR-300 was significantly down-regulated in melanoma cells (log FC = -1.63) and exosomes (log FC = -1.34). Among the transcription factors predicted to regulate miR-300, MYC, PPARG, and ZIC2 were significantly up-regulated in melanoma cells, and TP53, JUN, JUNB, FOS, and FOSB interacted with GADD45B. We attempted to reveal the pathogenesis of melanoma and screen new biomarkers by constructing a TF-mRNA-miRNA axis in turn to provide a view for further research.
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PMID:MicroRNA-300: A Transcellular Mediator in Exosome Regulates Melanoma Progression. 3168 65

Esophageal cancer is one of the most common cancer with limited therapeutic strategies, thus it is important to develop more effective strategies to against it. Sulforaphene (SFE), an isothiocyanate isolated from radish seeds, was proved to inhibit esophageal cancer progression in the current study. Flow cytometric analysis showed SFE induced cell apoptosis and cycle arrest in G2/M phase. Also, scrape motility and transwell assays presented SFE reduced esophageal cancer cell metastasis. Microarray results showed the influence of SFE on esophageal cancer cells was related with stearoyl-CoA desaturase (SCD), cadherin 3 (CDH3), mitogen-activated protein kinase kinase 3 (MAP2K3) and growth arrest and DNA damage inducible beta (GADD45B). SCD and CDH3 could promote esophageal cancer metastasis via activating the Wnt pathway, while the latter one was involved in a positive feedback loop, GADD45B-MAP2K3-p38-p53, to suppress esophageal cancer growth. GADD45B was known to be the target gene of p53, and we proved in this study, it could increase the phosphorylation level of MAP2K3 in esophageal cancer cells, activating p38 and p53 in turn. SFE treatment elevated MAP2K3 and GADD45B expression and further stimulated this feedback loop to better exert antitumor effect. In summary, these results demonstrated that SFE had the potential for developing as a chemotherapeutic agent because of its inhibitory effects on esophageal cancer metastasis and proliferation.
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PMID:Sulforaphene inhibits esophageal cancer progression via suppressing SCD and CDH3 expression, and activating the GADD45B-MAP2K3-p38-p53 feedback loop. 3287 75


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