scholarly journals MicroRNA-125b Promotes Neuronal Differentiation in Human Cells by Repressing Multiple Targets

2009 ◽  
Vol 29 (19) ◽  
pp. 5290-5305 ◽  
Author(s):  
Minh T. N. Le ◽  
Huangming Xie ◽  
Beiyan Zhou ◽  
Poh Hui Chia ◽  
Pamela Rizk ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Neural Development ◽  
Ectopic Expression ◽  
Global Changes ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Mrna Targets

ABSTRACT MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression at the posttranscriptional level. Research on miRNAs has highlighted their importance in neural development, but the specific functions of neurally enriched miRNAs remain poorly understood. We report here the expression profile of miRNAs during neuronal differentiation in the human neuroblastoma cell line SH-SY5Y. Six miRNAs were significantly upregulated during differentiation induced by all-trans-retinoic acid and brain-derived neurotrophic factor. We demonstrated that the ectopic expression of either miR-124a or miR-125b increases the percentage of differentiated SH-SY5Y cells with neurite outgrowth. Subsequently, we focused our functional analysis on miR-125b and demonstrated the important role of this miRNA in both the spontaneous and induced differentiations of SH-SH5Y cells. miR-125b is also upregulated during the differentiation of human neural progenitor ReNcell VM cells, and miR-125b ectopic expression significantly promotes the neurite outgrowth of these cells. To identify the targets of miR-125b regulation, we profiled the global changes in gene expression following miR-125b ectopic expression in SH-SY5Y cells. miR-125b represses 164 genes that contain the seed match sequence of the miRNA and/or that are predicted to be direct targets of miR-125b by conventional methods. Pathway analysis suggests that a subset of miR-125b-repressed targets antagonizes neuronal genes in several neurogenic pathways, thereby mediating the positive effect of miR-125b on neuronal differentiation. We have further validated the binding of miR-125b to the miRNA response elements of 10 selected mRNA targets. Together, we report here for the first time the important role of miR-125b in human neuronal differentiation.

Role of GST P1-1 in mediating the effect of etoposide on human neuroblastoma cell line Sh-Sy5y

2002 ◽  
Vol 86 (2) ◽  
pp. 340-347 ◽  
Author(s):  
S. Bernardini ◽  
L. Bellincampi ◽  
S. Ballerini ◽  
M. Ranalli ◽  
A. Pastore ◽  
...  
Keyword(s):  
Cell Line ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Human Neuroblastoma Cell Line

Ciliary neurotrophic factor-induced gene expression in human neuroblastoma cell lines

1995 ◽  
Vol 20 (6) ◽  
pp. 675-680 ◽  
Author(s):  
P. Rossino ◽  
G. Volpe ◽  
A. Negro ◽  
L. Callegaro ◽  
F. Altruda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Neurotrophic Factor ◽  
Neuroblastoma Cell ◽  
Ciliary Neurotrophic Factor ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Neuroblastoma Cell Lines

Expression and function of TRK-B and BDNF in human neuroblastomas

1994 ◽  
Vol 14 (1) ◽  
pp. 759-767
Author(s):  
A Nakagawara ◽  
C G Azar ◽  
N J Scavarda ◽  
G M Brodeur
Keyword(s):  
Neurite Outgrowth ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cell Line ◽  
Human Neuroblastoma Cell ◽  
Bdnf Mrna ◽  
Human Neuroblastoma ◽  
Pediatric Tumor ◽  
Trk A ◽  
High Level ◽  
Trk B

There is considerable interest in the role of the TRK family of neuotrophin receptors in regulating growth and differentiation in normal and neoplastic nerve cells. A neuroblastoma is a common pediatric tumor derived from the neural crest, and the majority of favorable neuroblastomas express a high level of TRK-A mRNA. However, little is known about the expression or function of TRK-B in these tumors. TRK-B encodes a tyrosine kinase that binds to brain-derived neuotrophic factor (BDNF), as well as neurotrophin-3 (NT-3) and NT-4/5. We have studied the N-myc-amplified human neuroblastoma cell line, SMS-KCN, which expresses both TRK-B and BDNF. Exogenous BDNF induces tyrosine phosphorylation of TRK-B as well as phosphorylation of phospholipase C-gamma 1, the extracellular signal-regulated kinases 1 and 2, and phosphatidylinositol-3 kinase. BDNF also induces expression of the immediate-early genes c-FOS and NGFI-A but not NGFI-B or NGFI-C. In addition, BDNF appears to promote cell survival and neurite outgrowth. SMS-KCN cells also express TRK-A, which is phosphorylated in response to nerve growth factor. However, the downstream TRK-A signaling is apparently defective. Finally, we determined that in a series of 74 primary neuroblastomas, 36% express TRK-B mRNA, 68% express BDNF mRNA, and 31% express both. Truncated TRK-B appears to be preferentially expressed in more-differentiated tumors (ganglioneuromas and ganglioneuroblastomas), whereas full-length TRK-B is expressed almost exclusively in immature neuroblastomas with N-myc amplification. Our findings suggest that in TRK-B-expressing human neuroblastomas, BDNF promotes survival and induces neurite outgrowth in an autocrine or paracrine manner. The BDNF/TRK-B pathway may be particularly important for growth and differentiation of neuroblastomas with N-myc amplification.

scholarly journals Trans-activation of the human SOX3 promoter by MAZ in NT2/D1 cells

2008 ◽  
Vol 60 (3) ◽  
pp. 379-387 ◽  
Author(s):  
Natasa Kovacevic-Grujicic ◽  
Kazunari Yokoyama ◽  
Milena Stevanovic
Keyword(s):  
Gene Expression ◽  
Neuronal Differentiation ◽  
Gene Transcription ◽  
Binding Sites ◽  
Promoter Activity ◽  
Zinc Finger Protein ◽  
Mobility Shift ◽  
Finger Protein ◽  
Sox3 Gene

In this study, we examine the role of three highly conserved putative binding sites for Myc-associated zinc finger protein (MAZ) in regulation of the human SOX3 gene expression. Electrophoretic mobility shift and supershift assays indicate that complexes formed at two out of three MAZ sites of the human SOX3 promoter involve ubiquitously expressed MAZ protein. Furthermore, in cotransfection experiments we demonstrate that MAZ acts as a positive regulator of SOX3 gene transcription in both undifferentiated and RA-differentiated NT2/D1 cells. Although MAZ increased both basal and RA-induced promoter activity, our results suggest that MAZ does not contribute to RA inducibility of the SOX3 promoter during neuronal differentiation of NT2/D1 cells.

Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells

2000 ◽  
Vol 113 (15) ◽  
pp. 2705-2713
Author(s):  
K. Sawada ◽  
Y. Konishi ◽  
M. Tominaga ◽  
Y. Watanabe ◽  
J. Hirano ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Mammalian Cells ◽  
Homeobox Gene ◽  
S Phase ◽  
Bhlh Transcription Factor ◽  
Spemann Organizer

In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.

Impact of persistent cytomegalovirus infection on human neuroblastoma cell gene expression

2005 ◽  
Vol 326 (2) ◽  
pp. 395-401 ◽  
Author(s):  
Gerold Hoever ◽  
Jens-Uwe Vogel ◽  
Polina Lukashenko ◽  
Wolf-Karsten Hofmann ◽  
Martina Komor ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cytomegalovirus Infection ◽  
Neuroblastoma Cell ◽  
Human Neuroblastoma Cell ◽  
Human Neuroblastoma ◽  
Cell Gene Expression ◽  
Cell Gene
Sign in / Sign up

Export Citation Format

Share Document