Abstract
MicroRNAs (MIRs) perform critical regulatory functions within cell networks, both in physiology as well as in pathology. Through the positional gene candidate approach, we have identified three MIRs (MIR152, MIR200B, and MIR338) that are located in regions frequently altered in neuroblastoma (NB) and target mRNAs encoding proteins involved in cell proliferation, neuroblast differentiation, neuroblast migration, and apoptosis. Expression analysis in NB biopsies and NB cell lines showed that these MIRs are dysregulated. We have characterized a CpG island, close to the gene encoding MIR200B and hypermethylated in NB samples, that explains its negative regulation. Expression of MIR152, MIR200B, and MIR338 is specifically modulated in NB cell lines during differentiation and apoptosis. Functional genomic experiments through enforced expression of MIR200B and knockdown of MIR152 resulted in a significant decrease of the invasion activity of SH-SY5Y cells. Reconstruction of a NB network comprising MIR152, MIR200B, and MIR338 allowed us to confirm their role in the control of NB cell stemness and apoptosis: This suggests that altered regulation of these MIRs could have a role in NB pathogenesis by interfering with the molecular mechanisms, which physiologically control differentiation and death of neuroblasts. Accordingly, they could be considered as new NB biomarkers and potential targets of antagomirs or epigenetic therapies.
| Original language | English |
|---|---|
| Pages (from-to) | 1041-1053 |
| Number of pages | 13 |
| Journal | Journal of Molecular Medicine |
| Volume | 88 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2010 |
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Keywords
- Cell networks
- Cell proliferation
- Genome imbalance
- MicroRNA
- Neuroblast apoptosis
- Neuroblast differentiation
- Neuroblast migration
- Neuroblastoma
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
- Genetics(clinical)
Cite this
MIR152, MIR200B, and MIR338, human positional and functional neuroblastoma candidates, are involved in neuroblast differentiation and apoptosis. / Ragusa, Marco; Majorana, Alessandra; Banelli, Barbara; Barbagallo, Davide; Statello, Luisa; Casciano, Ida; Guglielmino, Maria Rosa; Duro, Laura Rita; Scalia, Marina; Magro, Gaetano; Di Pietro, Cinzia; Romani, Massimo; Purrello, Michele.
In: Journal of Molecular Medicine, Vol. 88, No. 10, 10.2010, p. 1041-1053.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MIR152, MIR200B, and MIR338, human positional and functional neuroblastoma candidates, are involved in neuroblast differentiation and apoptosis
AU - Ragusa, Marco
AU - Majorana, Alessandra
AU - Banelli, Barbara
AU - Barbagallo, Davide
AU - Statello, Luisa
AU - Casciano, Ida
AU - Guglielmino, Maria Rosa
AU - Duro, Laura Rita
AU - Scalia, Marina
AU - Magro, Gaetano
AU - Di Pietro, Cinzia
AU - Romani, Massimo
AU - Purrello, Michele
PY - 2010/10
Y1 - 2010/10
N2 - MicroRNAs (MIRs) perform critical regulatory functions within cell networks, both in physiology as well as in pathology. Through the positional gene candidate approach, we have identified three MIRs (MIR152, MIR200B, and MIR338) that are located in regions frequently altered in neuroblastoma (NB) and target mRNAs encoding proteins involved in cell proliferation, neuroblast differentiation, neuroblast migration, and apoptosis. Expression analysis in NB biopsies and NB cell lines showed that these MIRs are dysregulated. We have characterized a CpG island, close to the gene encoding MIR200B and hypermethylated in NB samples, that explains its negative regulation. Expression of MIR152, MIR200B, and MIR338 is specifically modulated in NB cell lines during differentiation and apoptosis. Functional genomic experiments through enforced expression of MIR200B and knockdown of MIR152 resulted in a significant decrease of the invasion activity of SH-SY5Y cells. Reconstruction of a NB network comprising MIR152, MIR200B, and MIR338 allowed us to confirm their role in the control of NB cell stemness and apoptosis: This suggests that altered regulation of these MIRs could have a role in NB pathogenesis by interfering with the molecular mechanisms, which physiologically control differentiation and death of neuroblasts. Accordingly, they could be considered as new NB biomarkers and potential targets of antagomirs or epigenetic therapies.
AB - MicroRNAs (MIRs) perform critical regulatory functions within cell networks, both in physiology as well as in pathology. Through the positional gene candidate approach, we have identified three MIRs (MIR152, MIR200B, and MIR338) that are located in regions frequently altered in neuroblastoma (NB) and target mRNAs encoding proteins involved in cell proliferation, neuroblast differentiation, neuroblast migration, and apoptosis. Expression analysis in NB biopsies and NB cell lines showed that these MIRs are dysregulated. We have characterized a CpG island, close to the gene encoding MIR200B and hypermethylated in NB samples, that explains its negative regulation. Expression of MIR152, MIR200B, and MIR338 is specifically modulated in NB cell lines during differentiation and apoptosis. Functional genomic experiments through enforced expression of MIR200B and knockdown of MIR152 resulted in a significant decrease of the invasion activity of SH-SY5Y cells. Reconstruction of a NB network comprising MIR152, MIR200B, and MIR338 allowed us to confirm their role in the control of NB cell stemness and apoptosis: This suggests that altered regulation of these MIRs could have a role in NB pathogenesis by interfering with the molecular mechanisms, which physiologically control differentiation and death of neuroblasts. Accordingly, they could be considered as new NB biomarkers and potential targets of antagomirs or epigenetic therapies.
KW - Cell networks
KW - Cell proliferation
KW - Genome imbalance
KW - MicroRNA
KW - Neuroblast apoptosis
KW - Neuroblast differentiation
KW - Neuroblast migration
KW - Neuroblastoma
UR - http://www.scopus.com/inward/record.url?scp=78149410101&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78149410101&partnerID=8YFLogxK
U2 - 10.1007/s00109-010-0643-0
DO - 10.1007/s00109-010-0643-0
M3 - Article
C2 - 20574809
AN - SCOPUS:78149410101
VL - 88
SP - 1041
EP - 1053
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
SN - 0946-2716
IS - 10
ER -