Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NMP-1 was initially identified as a nuclear matrix-associated DNA-binding factor that exhibits sequence-specific recognition for the site IV regulatory element of a histone H4 gene. This distal promoter domain is a nuclear matrix interaction site. In the present study, we show that NMP-1 is the multifunctional transcription factor YY1. Gel-shift and Western blot analyses demonstrate that NMP-1 is immunoreactive with YY1 antibody. Furthermore, purified YY1 protein specifically recognizes site IV and reconstitutes the NMP-1 complex. Western blot and gel-shift analyses indicate that YY1 is present within the nuclear matrix. In situ immunofluorescence studies show that a significant fraction of YY1 is localized in the nuclear matrix, principally but not exclusively associated with residual nucleoli. Our results confirm that NMP-1/YY1 is a ubiquitous protein that is present in both human cells and in rat osteosarcoma ROS 17/2.8 cells. The finding that NMP-1 is identical to YY1 suggests that this transcriptional regulator may mediate gene-matrix interactions. Our results are consistent with the concept that the nuclear matrix may functionally compartmentalize the eukaryotic nucleus to support regulation of gene expression.
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PMID:The nuclear matrix protein NMP-1 is the transcription factor YY1. 747 33

Bone sialoprotein (BSP) is a noncollagenous matrix glycoprotein localized predominantly in mineralized tissues but also detected in extraskeletal sites undergoing focal mineralization. We have previously characterized the human BSP gene and have shown that the upstream sequence contains inverted TATA and CCAAT motifs at the expected locations from the transcriptional start site (J. M. Kerr et al. [13]) and a potential YY1 binding motif located within the first 30 bp of intron 1 of the human gene. Deletion analyses of the human BSP promoter/exon 1 sequence fused to a CAT reporter gene indicate that CCAAT enhances basal transcription of BSP in transiently transfected rat UMR106-01 BSP osteosarcoma and rat skin fibroblasts. Though this enhancing activity was lost with inclusion of 68 bp of intron containing a YY1 motif in these constructs, reporter activity in the UMR106-01-BSP cells was elevated four- to seven-fold relative to that of rat fibroblasts. Gel electrophoretic mobility shift, UV-crosslinking, and south-western experiments indicate that YY1 is present only in the extracts of nuclei isolated from the UMR cells and may contribute to the elevated transcriptional activity of the human BSP promoter construct in UMR106-01-BSP.
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PMID:The human bone sialoprotein gene contains an NF-E1/YY1 cis-acting sequence with putative regulatory activity. 906 66

The multifunctional transcription factor YY1 is associated with the nuclear matrix. In osteoblasts, the interaction of several nuclear matrix-associated transcription factors with the bone specific osteocalcin gene contributes to tissue-specific and steroid hormone-mediated transcription. A canonical nuclear matrix targeting signal (NMTS) is present in all members of the AML/CBFbeta transcription factor family, but not in other transcription factors. Therefore, we defined sequences that direct YY1 (414 amino acids) to the nuclear matrix. A series of epitope tagged deletion constructs were expressed in HeLa S3 and in human Saos-2 osteosarcoma cells. Subcellular distribution was determined in whole cells and nuclear matrices in situ by immunofluorescence. We demonstrated that amino acids 257-341 in the C-terminal domain of YY1 are necessary for nuclear matrix association. We also observed that sequences within the N-terminal domain of YY1 permit weak nuclear matrix binding. Our data further suggest that the Gal4 epitope tag contains sequences that affect subcellular localization, but not targeting to the nuclear matrix. The targeted association of YY1 with the nuclear matrix provides an additional level of functional regulation for this transcription factor that can exhibit positive and negative control.
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PMID:Targeting of the YY1 transcription factor to the nucleolus and the nuclear matrix in situ: the C-terminus is a principal determinant for nuclear trafficking. 949 12

We show that human osteosarcoma cells (Saos-2) have downregulation of alpha3beta1-integrin compared to normal bone cells; this was further described in human osteosarcomas and in a primary murine sarcoma. The alpha3 gene was silenced in Saos-2 cells causing a low expression of alpha3beta1-integrin and reduction in collagen attachment with increasing migratory capacity. Chromatin immunoprecipitation assay performed on alpha3 promoter established that Myc and Yin Yang protein (YY1) cooperate in tandem to downregulate the alpha3 gene. This silencing mechanism involves the binding of Myc and YY1 to DNA and formation of complexes among Myc/Max, YY1, CREB-binding protein and deacetylation activity. The promoter containing deletions of E-boxes or YY1 cassettes failed to downregulate the transcription of a reporter gene as well as the inhibition of deacetylation activity. Overexpression of both Myc and YY1 was necessary to determine the alpha3-integrin promoter downregulation in normal osteoblasts. This downregulation of alpha3beta1-integrin can contribute to the acquisition of a more aggressive phenotype. YY1 regulated negatively the Myc activity through a direct interaction with the Myc/Max and deacetylase complexes. This represents a novel silencing mechanism with broad implications in the transcription machinery of tumours.
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PMID:Cooperation between Myc and YY1 provides novel silencing transcriptional targets of alpha3beta1-integrin in tumour cells. 1687 56

RIZ1 isoform, but not RIZ2, is commonly silenced in many types of tumors. In osteosarcoma cells, RIZ1 protein is very abundant. The silencing of YY1 protein, a recent target gene in osteosarcoma cells, reduced the expression of RIZ1 protein. Here we show that RIZ1 overexpression is a transcriptional event documented by Western blot, RT-PCR, and promoter assays. YY1 protein binds and cooperates to positive regulation of the RIZ1 promoter and its presence reduced the dimethyl lysine 9 histone 3 by chromatin immunoprecipitation assays. These results indicate that overexpression of YY1 in osteosarcoma cells plays a key role in positive regulation of RIZ1. The coexpression of RIZ1/YY1 proteins suggests a tandem regulatory mechanism in human osteosarcoma cells and tissues.
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PMID:Silencing of YY1 downregulates RIZ1 promoter in human osteosarcoma. 1848 13

Previous work demonstrated that exogenous expression of Rybp (Ring 1 YY1-binding protein or DEDAF) kills tumor but not non-transformed cells. This tumor-preferential killing activity could be exploited in a gene therapy approach to treat cancer. To test the potential of viral-mediated delivery of Rybp as an anticancer treatment, we generated an adenovirus expressing Rybp (Ad-Rybp). Infection with Ad-Rybp inhibits the proliferation of a range of tumor cell lines, but has no effect on normal cell types. This inhibition of proliferation is the result of the induction of apoptosis, consistent with reports that Rybp regulates apoptosis. Combined Ad-Rybp infection and etoposide treatment resulted in an additive cytotoxic effect in the osteosarcoma cell line U20S. Furthermore, Ad-Rybp infection synergistically cooperates with the death receptor ligand, tumor necrosis factor-alpha, in the induction of apoptosis. These results suggest that Ad-Rybp may have clinical applicability, either alone or in combination with other agents for the treatment of cancer.
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PMID:Adenoviral-mediated Rybp expression promotes tumor cell-specific apoptosis. 1855 Nov 46

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

Mounting research papers have suggested that long non-coding RNAs (lncRNAs) elicit important functions in the progression of osteosarcoma (OS). This study focused on the role of TNK2-AS1 in OS. TNK2-AS1 was powerfully expressed in OS tissues and cell lines. In addition, TNK2-AS1 downregulation inhibited proliferative, migratory, and invasive capacities while promoting apoptosis in OS cells. miR-4319 was removed by TNK2-AS1 and therefore TNK2-AS1 elevated WDR1 expression in OS cells. miR-4319 had an inhibitory influence on OS progression, while WDR1 was a contributor to OS progression. Rescue assays certified that TNK2-AS1 promoted malignant phenotypes in vitro and the growth in vivo of OS cells by upregulating WDR1. In depth, we found that YY1 accelerated the transcription of TNK2-AS1 in OS cells, and that its role in OS also depended on TNK2-AS1-regulated WDR1. In conclusion, TNK2-AS1 was positively modulated by YY1 and aggravated the development of OS by 'sponging' miR-4319 to elevate WDR1. The findings highlighted that TNK2-AS1 might be a promising target for the treatment of OS.
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PMID:TNK2-AS1 upregulated by YY1 boosts the course of osteosarcoma through targeting miR-4319/WDR1. 3316 71