MYCN oncogene is one of the most important regulators affecting the prognosis of neuroblastoma and is frequently amplified in the high-risk subsets. Despite its clinical significance, it remains unclear how the MYCN expression is regulated in human neuroblastomas. Here, we found the presence of a positive auto-regulatory mechanism of MYCN. Enforced expression of MYCN induced endogenous MYCN mRNA expression in SK-N-AS neuroblastoma cells with a single copy of MYCN gene. Luciferase reporter assay revealed that MYCN protein activates its own promoter activity in a dose-dependent manner and the downstream region relative to the transcription start sites is responsible for the activation. Furthermore, ChIP analysis showed that MYCN is directly recruited onto the intron 1 region of MYCN gene which contains two putative E-box sites. Intriguingly, in response to all-trans-retinoic acid (ATRA), MYCN was down-regulated in MYCN-amplified SK-N-BE neuroblastoma cells, and the recruitment of MYCN protein onto its own intron 1 region was reduced in association with an induction of neuronal differentiation. Collectively, our present results suggest that MYCN contributes to its own expression by forming a positive auto-regulatory loop in neuroblastoma cells.
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http://dx.doi.org/10.1016/j.bbrc.2009.09.044 | DOI Listing |
Genes Dis
March 2025
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA.
Targeting oncogenes and their interactive partners is an effective approach to developing novel targeted therapies for cancer and other chronic diseases. We and others have long suggested the MDM2 oncogene being an excellent target for cancer therapy, based on its p53-dependent and -independent oncogenic activities in a variety of cancers. The MYC family proteins are transcription factors that also regulate diverse biological functions.
View Article and Find Full Text PDFBMC Ecol Evol
January 2025
College of Life Sciences, Qufu Normal University, Qufu, 273165, China.
Background: Semi-aquatic mammals represent a transitional phase in the evolutionary spectrum between terrestrial and aquatic mammals. The sense of balance is crucial for mammalian locomotion, and in semi-aquatic mammals, the structural foundation of this sense (the vestibular system) shows distinct morphological adaptations to both aquatic and terrestrial environments compared to their terrestrial counterparts. Despite this, the precise molecular mechanisms driving these adaptations remain elusive.
View Article and Find Full Text PDFRev Esp Patol
January 2025
Departamento de Patología, Universidad de Valencia, Hospital Clínico Universitario de Valencia, CIBERONC (ISCIII Madrid), INCLIVA, Valencia, Spain. Electronic address:
High-risk neuroblastoma continues to show a very high mortality, with a 5-year survival rate of 50%. While MYCN amplification is the main genetic alteration associated with high-risk tumours, other molecular mechanisms, such as alterations in ATRX and TERT, remain poorly understood. ATRX and TERT biomarkers, which are associated with a more aggressive neuroblastoma pattern, should be considered for accurate prognostic stratification.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Department of Pathology, Deyang Peoples' Hospital, Deyang, Sichuan Province, China.
Rationale: Ependymomas are commonly prevalent intramedullary neoplasms in adults, with hardly any cases of exophytic extramedullary ependymoma being reported. Meningiomas, on the contrary, are one of the most common intradural extramedullary (IDEM) tumors. However, the occurrence of both IDEM tumors simultaneously is extremely rare.
View Article and Find Full Text PDFCancer Res
December 2024
Lunenfeld-Tanenbaum Research Institute, Toronto, Canada.
IDH-mutant low-grade gliomas (LGGs) are slow-growing brain tumors that frequently progress to aggressive high-grade gliomas that have dismal outcomes. In a recent study, Wu and colleagues provide critical insights into the mechanisms underlying malignant progression by analyzing single-cell gene expression and chromatin accessibility across different tumor grades. Their findings support a two-phase model: in early stages, tumors are primarily driven by oligodendrocyte precursor-like cells and epigenetic alterations that silence tumor suppressors like CDKN2A and activate oncogenes such as PDGFRA.
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