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Promoter hypermethylation as a mechanism for Lamin A/C silencing in a subset of neuroblastoma cells
- Source :
- PLoS ONE, COLIBRI, Universidad de la República, instacron:Universidad de la República, PLoS ONE, Vol 12, Iss 4, p e0175953 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science, 2017.
-
Abstract
- Nuclear lamins support the nuclear envelope and provide anchorage sites for chromatin. They are involved in DNA synthesis, transcription, and replication. It has previously been reported that the lack of Lamin A/C expression in lymphoma and leukaemia is due to CpG island promoter hypermethylation. Here, we provide evidence that Lamin A/C is silenced via this mechanism in a subset of neuroblastoma cells. Moreover, Lamin A/C expression can be restored with a demethylating agent. Importantly, Lamin A/C reintroduction reduced cell growth kinetics and impaired migration, invasion, and anchorage-independent cell growth. Cytoskeletal restructuring was also induced. In addition, the introduction of lamin Δ50, known as Progerin, caused senescence in these neuroblastoma cells. These cells were stiffer and developed a cytoskeletal structure that differed from that observed upon Lamin A/C introduction. Of relevance, short hairpin RNA Lamin A/C depletion in unmethylated neuroblastoma cells enhanced the aforementioned tumour properties. A cytoskeletal structure similar to that observed in methylated cells was induced. Furthermore, atomic force microscopy revealed that Lamin A/C knockdown decreased cellular stiffness in the lamellar region. Finally, the bioinformatic analysis of a set of methylation arrays of neuroblastoma primary tumours showed that a group of patients (around 3%) gives a methylation signal in some of the CpG sites located within the Lamin A/C promoter region analysed by bisulphite sequencing PCR. These findings highlight the importance of Lamin A/C epigenetic inactivation for a subset of neuroblastomas, leading to enhanced tumour properties and cytoskeletal changes. Additionally, these findings may have treatment implications because tumour cells lacking Lamin A/C exhibit more aggressive behaviour.
- Subjects :
- 0301 basic medicine
Bisulfite sequencing
lcsh:Medicine
Biochemistry
Small hairpin RNA
Neuroblastoma
0302 clinical medicine
Mathematical and Statistical Techniques
Contractile Proteins
Neural Stem Cells
Cell Movement
Medicine and Health Sciences
Blastomas
RNA, Small Interfering
lcsh:Science
Promoter Regions, Genetic
Cytoskeleton
Cultured Tumor Cells
Neurons
Microscopy
Multidisciplinary
DNA methylation
biology
integumentary system
Chemistry
Brain Neoplasms
Retinoblastoma protein
Progerin
Lamin Type A
Lamins
Chromatin
Atomic Force Microscopy
Curve Fitting
Nucleic acids
Gene Expression Regulation, Neoplastic
Actin Cytoskeleton
Oncology
030220 oncology & carcinogenesis
embryonic structures
Nuclear lamina
Epigenetics
Biological Cultures
Cellular Structures and Organelles
DNA modification
Neuroglia
Chromatin modification
Research Article
Chromosome biology
Signal Transduction
congenital, hereditary, and neonatal diseases and abnormalities
Cell biology
animal structures
Primary Cell Culture
Research and Analysis Methods
Syndrome HGPS
Cell Line
03 medical and health sciences
Cell Line, Tumor
Genetics
Humans
Gene Silencing
Cell Proliferation
Base Sequence
Scanning Probe Microscopy
lcsh:R
Biology and Life Sciences
Proteins
Cancers and Neoplasms
DNA
Cell Cultures
Molecular biology
Actins
Cytoskeletal Proteins
030104 developmental biology
biology.protein
Neuroblastoma Cells
lcsh:Q
CpG Islands
Gene expression
Mathematical Functions
Lamin
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....1b1ae8dd2ab0ef6b89ab59f04a79d490