Dataset Information

Sam68 is a novel marker for aggressive neuroblastoma.

ABSTRACT: BACKGROUND:Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism and progression of NB is largely unknown, and unfortunately, the prognosis is poor. Src-associated in mitosis with a molecular weight of 68 kDa (Sam68) is associated with carcinogenesis and neurogenesis. The present study aimed to investigate the clinical and prognostic significance of Sam68 in NB. METHODS:The expression of Sam68 in immortalized normal epithelial cells, NB cell lines, and in four cases of paired NB tissue and adjacent normal tissue from the same patient was examined using Western blotting, reverse transcription-polymerase chain reaction (PCR) and real-time reverse transcription-PCR. The proliferation of NB cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, Sam68 protein expression was analyzed in 90 NB cases characterized as clinicopathological using immunohistochemistry. Statistical analyses were applied to evaluate the diagnostic value and associations of Sam68 with clinical parameters. RESULTS:Western blotting and reverse transcription-PCR showed that the expression level of Sam68 was markedly higher in NB cell lines than in the immortalized normal epithelial cells at both messenger RNA and protein levels. The MTT assay revealed that Sam68 expression supported proliferation of NB cells. Sam68 expression levels were significantly up-regulated in tumor tissues in comparison to the matched adjacent normal tissues from the same patient. Sam68 protein level was positively correlated with clinical stage (P<0.001), tumor histology (P<0.001), and distant metastasis (P=0.029). Patients with higher Sam68 expression had shorter overall survival time, whereas those with lower tumor Sam68 expression had longer survival time. CONCLUSION:Our results suggest that Sam68 expression is associated with neuroblastoma progression and may represent a novel and valuable predictor for prognostic evaluation of neuroblastoma patients.

SUBMITTER: Zhao X

PROVIDER: S-EPMC3855102 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sam68 is a novel marker for aggressive neuroblastoma.

Zhao Xiaohong X Li Zuoqing Z He Benfu B Liu Juncheng J Li Suisheng S Zhou Li L Pan Cuiling C Yu Zhe Z Xu Zhe Z

OncoTargets and therapy 20131202

<h4>Background</h4>Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism and progression of NB is largely unknown, and unfortunately, the prognosis is poor. Src-associated in mitosis with a molecular weight of 68 kDa (Sam68) is associated with carcinogenesis and neurogenesis. The present study aimed to investigate the clinical and prognostic significance of Sam68 in NB.<h4>Methods</h4>The expression of Sam68 in immortalized normal epithelial ...[more]

PMID: 24324342

Similar Datasets

Project description:BackgroundNeuroblastoma (NB) is one of the deadliest paediatric solid tumours due to its rapid proliferative characteristics. Amplified copies of MYCN are considered the most important marker for the prediction of tumour relapse and progression in NB, but they were only detected in 20-30% of NB patients, indicating there might be other oncogenes in the development of NB. The far upstream element binding protein 1 (FUBP1) was first identified as a transcriptional regulator of the proto-oncogene MYC. However, the expression and role of FUBP1 in NB have not been documented.MethodsFUBP1 expression was analysed from GEO database and verified by immunohistochemistry (IHC) and western blotting (WB) in NB tissues and cell lines. Cell proliferation and apoptosis were detected by Cell Counting Kit-8, Colony formation assay, EDU, TUNEL staining and flow cytometric analysis. Several glycolytic metabolites production was confirmed by ELISA and oxygen consuming rate (OCR). Luciferase assay, WB, chromatin immunoprecipitation (CHIP) were used to explore the mechanisms of the effect of FUBP1 on NB.ResultsFUBP1 mRNA levels were increased along with the increase in International Neuroblastoma Staging System (INSS) stages. High expression of FUBP1 with low N-Myc expression accounted for 44.6% of NB patient samples (n = 65). In addition, FUBP1 protein levels were remarkably increased with NB malignancy in the NB tissue microarray (NB: n = 65; ganglioneuroblastoma: n = 31; ganglioneuroma: n = 27). Furthermore, FUBP1 expression was negatively correlated with patient survival rate but positively correlated with ki67 content. In vitro experiments showed that FUBP1 promotes NB cell proliferation and inhibits cell apoptosis via enhancing glycolysis and ATP production. Mechanistically, FUBP1 inhibited the degradation of HIF1α via downregulation of Von Hippel-Lindau (VHL), the E3 ligase for HIF1α, resulting in upregulation of lactate dehydrogenase isoform B (LDHB) expression to enhance glycolysis. Overexpressed or silenced N-Myc could not regulate FUBP1 or LDHB levels.ConclusionsTaken together, our findings demonstrate for the first time that elevated FUBP1 promotes NB glycolysis and growth by targeting HIF1α rather than N-Myc, suggesting that FUBP1 is a novel and powerful oncogene in the development of NB independent of N-Myc and may have potential in the diagnosis and treatment of NB.

Dataset Information

Sam68 is a novel marker for aggressive neuroblastoma.

Publications

Sam68 is a novel marker for aggressive neuroblastoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets