Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A growing number of reports indicate the frequent presence of DNA sequences and gene products of human cytomegalovirus in various tumors as compared to adjacent normal tissues, the brain tumors being studied most intensely. The mechanisms underlying the tropism of human cytomegalovirus to the tumor cells or to the cells of tumor origin, as well as the role of the host's genetic background in virus-associated oncogenesis are not well understood. It is also not clear why cytomegalovirus can be detected in many but not in all tumor specimens. Our in silico prediction results indicate that microRNA-34a may be involved in replication of some human DNA viruses by targeting and downregulating the genes encoding a diverse group of proteins, such as platelet-derived growth factor receptor-alpha, complement component receptor 2, herpes simplex virus entry mediators A, B, and C, and CD46. Notably, while their functions vary, these surface molecules have one feature in common: they serve as cellular entry receptors for human DNA viruses (cytomegalovirus, Epstein-Barr virus, human herpes virus 6, herpes simplex viruses 1 and 2, and adenoviruses) that are either proven or suspected to be linked with malignancies. MicroRNA-34a is strictly dependent on its transcriptional activator tumor suppressor protein p53, and both p53 and microRNA-34a are frequently mutated or downregulated in various cancers. We hypothesize that p53-microRNA-34a axis may alter susceptibility of cells to infection with some viruses that are detected in tumors and either proven or suspected to be associated with tumor initiation and progression.
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PMID:The p53-microRNA-34a axis regulates cellular entry receptors for tumor-associated human herpes viruses. 2364 4

ErbB2 is a vital breast cancer gene and its overexpression has a decisive role in breast tumor initiation and malignant progression. However, the molecular mechanisms that underlie ErbB2 dysregulation in breast cancer cells remain incompletely understood. In this study, we found that ErbB2 expression is inversely correlated with the level of miR-155, a well-documented oncogenic miRNA, in ErbB2-positive breast tumors. We further determined that miR-155 potently suppresses ErbB2 in breast cancer cells. Mechanistically, miR-155 acts to downregulate ErbB2 via two distinct mechanisms. First, miR-155 represses ErbB2 transcription by targeting HDAC2, a transcriptional activator of ErbB2. Second, miR-155 directly targets ErbB2 via a regulatory element in its coding region. Intriguingly, miR-155 is upregulated by trastuzumab and in turn leads to a reduction of ErbB2 expression in trastuzumab-treated ErbB2-positive breast cancer cells. Functional studies showed that miR-155 inhibits ErbB2-induced malignant transformation of human breast epithelial cells. Thus, our findings reveal an intriguing miR-155-ErbB2 context in regulating the malignant transformation of breast epithelial cells, and thereby indicate a novel mode of action for miR-155 in ErbB2-positive breast cancer.
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PMID:miR-155 downregulates ErbB2 and suppresses ErbB2-induced malignant transformation of breast epithelial cells. 2706 18