Reduced levels of miR‐34a in neuroblastoma are not caused by mutations in the <i>TP53</i> binding site

Feinberg-Gorenshtein, Galina; Avigad, Smadar; Jeison, Marta; Halevy-Berco, Gili; Mardoukh, Jacques; Luria, Drorit; Ash, Susan; Steinberg, Ran; Weizman, Abraham; Yaniv, Isaac

doi:10.1002/gcc.20662

Cited by 28 publications

(26 citation statements)

References 23 publications

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“…80, 114, 115). An additional parameter affecting miR-34a expression is its genomic status, as indicated by significant association between lower miR-34a levels and 1p36 deletion in neuroblastomas (116,117). In conclusion, miR-34a acts as a pivotal element in the p53 tumor suppressive pathway, and its recurrent downregulation by a broad range of mechanisms in various malignancies together with its inhibitory effect in cancer cell models suggests that aberrant reduction of miR-34a levels contributes to cancer development.…”

Section: Mir-34amentioning

confidence: 85%

1p36 Tumor Suppression—A Matter of Dosage?

2012

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A broad range of human malignancies is associated with nonrandom 1p36 deletions, suggesting the existence of tumor suppressors encoded in this region. Evidence for tumor-specific inactivation of 1p36 genes in the classic "two-hit" manner is scarce; however, many tumor suppressors do not require complete inactivation but contribute to tumorigenesis by partial impairment. We discuss recent data derived from both human tumors and functional cancer models indicating that the 1p36 genes CHD5, CAMTA1, KIF1B, CASZ1, and miR-34a contribute to cancer development when reduced in dosage by genomic copy number loss or other mechanisms. We explore potential interactions among these candidates and propose a model where heterozygous 1p36 deletion impairs oncosuppressive pathways via simultaneous downregulation of several dosage-dependent tumor suppressor genes. Cancer Res; 72(23); 6079-88. Ó2012 AACR.

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Section: Mir-34amentioning

confidence: 85%

1p36 Tumor Suppression—A Matter of Dosage?

2012

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“…16 Candidate tumor suppressors in this region include CDKN2C, 17 CAMTA1, 18 TNFRSF9, 19 CHD5, 20 TP73 21 and miR-34a. Abnormalities of miR-34a have been reported in neuroblastomas, 10,13,22,23 leukemias 24 and uveal melanomas, 25 as well as cancers of the colon, 26 prostate, 27 pancreas, 28 liver 29 and brain. 30,31 We identified two GBM samples with a small homozygous deletion localized at miR-34a (1p36.23), which only contained two other genes GPR157 and H6PD.…”

Section: Discussionmentioning

confidence: 99%

miR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme

et al. 2012

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Chromosome 1p36.23 is frequently deleted in glioblastoma multiforme (GBM). miR-34a localizes in this region. Our experiments found that miR-34a was often deleted and epidermal growth factor receptor (EGFR) was frequently amplified in genomic DNA of 55 GBMs using single-nucleotide polymorphism DNA microarray. Notably, we found that the mean survival time was significantly shortened for patients whose GBMs had both EGFR amplification and miR-34a deletion. Expression of miR-34a was significantly lower in GBM samples compared with normal brain tissue. Forced expression of miR-34a in GBM cells decreased their ability to migrate and profoundly decreased their levels of cyclin-A1, -B1, -D1, and -D3, as well as cyclin-dependent kinase and increased expression of cyclin kinase inhibitor proteins (p21, p27). Also, human GBM cells (U251) stable overexpressing mir-34a formed smaller tumors when growing as xenografts in immunodeficient mice compared with wild-type U251 GBM cells. Furthermore, the protein expression of EGFR decreased in the cells with forced overexpression of miR-34a. Additional studies showed that mir-34a targeted Yin Yang-1 (YY1) and YY1 is a transcription factor that can stimulate the expression of EGFR. Thus, our data suggest that miR-34a acts as a tumor suppressor by inhibiting growth of GBM cells in vitro and in vivo associated with moderating the expression of cell-cycle proteins and EGFR. Moreover, we discovered for the first time that both deletion of miR-34a and amplification of EGFR were associated with significantly decreased overall survival of GBM patients.

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“…As a star molecule, the expression of miR-34a was influenced by several factors, such as loss of 1p36 heterozygosity, the CpG island methylation of miR-34a genes and functional p53 [26,27]. In the apoptosis pathway, miR-34a was always believed to transduct the apoptosis signal from the p53 to other apoptosis related proteins, such as cell cycle arrest related genes Cyclin E, CDK4 and CDK6, and cell survival related genes Bcl-2 [28].…”

Section: Discussionmentioning

confidence: 99%

The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis

Lou

Liu

et al. 2015

Cell Physiol Biochem

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Background: The anti-tumor effects of quercetin have been reported, but the underlying molecular mechanisms remain to be elucidated. The aim of present study was to explore the role of miRNA in the anticancer effects of quercetin. Methods: The differential miRNAs expression between the HepG2 and Huh7 cells treated by quercetin were detected by microarray. The xCELLigence, Flow cytometry, RT-PCR and Western blot were used to analyze the cell proliferation, cell apoptosis, cell cycle arrest, anti-tumor genes, and protein expression. Results: miR-34a was up-regulated in HepG2 cells treated by quercetin exhibiting wild-type p53. When inhibiting the miR-34a, the sensitivity of the cells to quercetin decreased and the expression of the SIRT1 was up-regulated, but the acetylation of p53 and the expression of some genes related to p53 down-regulated. Conclusion: miR-34a plays an important role in the anti-tumor effects of querctin in HCC, miR-34a may be a tiemolecule between the p53 and SIRT1 and is composed of a p53/miR-34a/SIRT1 signal feedback loop, which could enhance apoptosis signal and significantly promote cell apoptosis.

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Reduced levels of miR‐34a in neuroblastoma are not caused by mutations in the TP53 binding site

Cited by 28 publications

References 23 publications

1p36 Tumor Suppression—A Matter of Dosage?

1p36 Tumor Suppression—A Matter of Dosage?

miR-34a functions as a tumor suppressor modulating EGFR in glioblastoma multiforme

The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis

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