Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies support the importance of microRNAs in physiological and pathological processes. Here we describe the regulation and function of miR-29 in myogenesis and rhabdomyosarcoma (RMS). Results demonstrate that in myoblasts, miR-29 is repressed by NF-kappaB acting through YY1 and the Polycomb group. During myogenesis, NF-kappaB and YY1 downregulation causes derepression of miR-29, which in turn accelerates differentiation by targeting its repressor YY1. However, in RMS cells and primary tumors that possess impaired differentiation, miR-29 is epigenetically silenced by an activated NF-kappaB-YY1 pathway. Reconstitution of miR-29 in RMS in mice inhibits tumor growth and stimulates differentiation, suggesting that miR-29 acts as a tumor suppressor through its promyogenic function. Together, these results identify a NF-kappaB-YY1-miR-29 regulatory circuit whose disruption may contribute to RMS.
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PMID:NF-kappaB-YY1-miR-29 regulatory circuitry in skeletal myogenesis and rhabdomyosarcoma. 1897 26

Rhabdomyosarcomas (RMS) express CXCR4 and CXCR7 receptors that bind prometastatic alpha-chemokine stromal-derived factor-1 (SDF-1). In this report, we analyzed the activity of both promoters in a model of less metastatic human embryonal-RMS cell line (RD) and more metastatic alveolar-like RMS (RD cells transduced with paired box gene 3/forkhead homologue; PAX3-FKHR fusion gene). First, CXCR4 is barely detectable in RD and becomes upregulated in RD/PAX3-FKHR cells. In contrast, CXCR7 highly expressed in RD becomes downregulated in RD/PAX3-FKHR cells. Next, promoter deletion and mutation studies revealed that whereas (a) expression of CXCR4 in RD and RD/PAX3-FKHR cells required nuclear respiratory factor-1 (NRF-1) binding site and (b) was additionally upregulated by direct interaction of NRF-1 with PAX3-FKHR, CXCR7 promoter activity required a proximal nuclear factor-kappaB-binding motif. The requirement of these factors for CXCR4 and CXCR7 promoter activities was additionally supported after blocking NRF-1 and nuclear factor-kappaB. Furthermore, CXCR4 expression in PAX3-FKHR(+) RMS cells seems to be enhanced because of the interaction of PAX3-FKHR and NRF-1 proteins in the proximal part of the promoter that prevents access of the negative regulator of transcription YY1 to its binding site. Finally, although hypoxia enhances CXCR4 and CXCR7 promoter activity and receptor expression in RD cells, it inhibits CXCR7 expression in RD/PAX3-FKHR cells. In conclusion, SDF-1 binding receptors CXCR4 and CXCR7 are differently regulated in RMS cells. The upregulation of CXCR4 and downregulation of CXCR7 expression by PAX3-FKHR or hypoxia may give SDF-1 an advantage to better engage the CXCR4 receptor, thus increasing RMS motility.
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PMID:Regulation of expression of stromal-derived factor-1 receptors: CXCR4 and CXCR7 in human rhabdomyosarcomas. 2006 66

The transcription factor Yin Yang (YY) 1 controls many divergent cellular processes, including cell proliferation and apoptosis. These are key to cancer development, as a consequence of which its expression has been studied in an increasingly wide range of human cancers, including lymphoma, breast, prostate, colon, ovarian, cervical, and brain cancers, osteosarcoma, rhabdomyosarcoma, and leukemia. It is a regulatory transcription factor for a wide range of genes, including genes involved in control of the cell cycle and apoptosis, and it can act either to upregulate or downregulate downstream gene expression, depending on the cellular environment, cofactors, and the gene targeted. Its expression has been associated with development of a malignant phenotype in some human cancers; tumor progression, including metastasis; and survival. However, as data on its prognostic significance has become available for more human cancers, its role in tumor progression has become controversial; there is conflicting data on its association with outcome, with some studies showing a favorable and others an unfavorable association. This is probably because of the many different roles YY1 plays in control of proliferation and apoptosis, one or the other of which may be more prominent in any given tumor. These studies are reviewed to give an overview of the increasingly recognized importance of YY1 in human tumorigenesis.
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PMID:Yin Yang 1 in human cancer. 2224 58