scholarly journals Transcriptional factor FoxM1-activated microRNA-335-3p maintains the self-renewal of neural stem cells by inhibiting p53 signaling pathway via Fmr1

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiaoying Jia ◽  
Yan Cui ◽  
Zhigang Tan ◽  
Min Liu ◽  
Yugang Jiang
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Signaling Pathway ◽  
Neurological Diseases ◽  
The Self ◽  
Self Renewal ◽  
P53 Signaling ◽  
Non Coding Rna ◽  
Fetal Rats ◽  
P53 Signaling Pathway

Abstract Background New mechanistic insights into the self-renewal ability and multipotent properties of neural stem cells (NSCs) are currently under active investigation for potential use in the treatment of neurological diseases. In this study, NSCs were isolated from the forebrain of fetal rats and cultured to induce NSC differentiation, which was associated with low expression of the non-coding RNA microRNA-335-3p (miR-335-3p). Methods Loss- and gain-of-function experiments were performed in NSCs after induction of differentiation. Results Overexpression of miR-335-3p or FoxM1 and inhibition of the Fmr1 or p53 signaling pathways facilitated neurosphere formation, enhanced proliferation and cell cycle entry of NSCs, but restricted NSC differentiation. Mechanistically, FoxM1 positively regulated miR-335-3p by binding to its promoter region, while miR-335-3p targeted and negatively regulated Fmr1. Additionally, the promotive effect of miR-335-3p on NSC self-renewal occurred via p53 signaling pathway inactivation. Conclusion Taken together, miR-335-3p activated by FoxM1 could suppress NSC differentiation and promote NSC self-renewal by inactivating the p53 signaling pathway via Fmr1.

scholarly journals Silencing of long noncoding RNA HOXA11-AS inhibits the Wnt signaling pathway via the upregulation of HOXA11 and thereby inhibits the proliferation, invasion, and self-renewal of hepatocellular carcinoma stem cells

2019 ◽  
Vol 51 (11) ◽  
pp. 1-20 ◽  
Author(s):  
Jun-Cheng Guo ◽  
Yi-Jun Yang ◽  
Jin-Fang Zheng ◽  
Jian-Quan Zhang ◽  
Min Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Wnt Signaling Pathway ◽  
The Self ◽  
Self Renewal

AbstractHepatocellular carcinoma (HCC) is a major cause of cancer-related deaths, but its molecular mechanisms are not yet well characterized. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis, including that of HCC. However, the role of homeobox A11 antisense (HOXA11-AS) in determining HCC stem cell characteristics remains to be explained; hence, this study aimed to investigate the effects of HOXA11-AS on HCC stem cell characteristics. Initially, the expression patterns of HOXA11-AS and HOXA11 in HCC tissues, cells, and stem cells were determined. HCC stem cells, successfully sorted from Hep3B and Huh7 cells, were transfected with short hairpin or overexpression plasmids for HOXA11-AS or HOXA11 overexpression and depletion, with an aim to study the influences of these mediators on the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo. Additionally, the potential relationship and the regulatory mechanisms that link HOXA11-AS, HOXA11, and the Wnt signaling pathway were explored through treatment with Dickkopf-1 (a Wnt signaling pathway inhibitor). HCC stem cells showed high expression of HOXA11-AS and low expression of HOXA11. Both HOXA11-AS silencing and HOXA11 overexpression suppressed the self-renewal, proliferation, migration, and tumorigenicity of HCC stem cells in vivo, as evidenced by the decreased expression of cancer stem cell surface markers (CD133 and CD44) and stemness-related transcription factors (Nanog, Sox2, and Oct4). Moreover, silencing HOXA11-AS inactivated the Wnt signaling pathway by decreasing the methylation level of the HOXA11 promoter, thereby inhibiting HCC stem cell characteristics. Collectively, this study suggested that HOXA11-AS silencing exerts an antitumor effect, suppressing HCC development via Wnt signaling pathway inactivation by decreasing the methylation level of the HOXA11 promoter.

scholarly journals Targeting the Hedgehog Signaling Pathway by Glasdegib Limits the Self- Renewal of MDS-Derived Induced Potent Stem Cells (iPSC)

2017 ◽  
Vol 09 (06) ◽  
Author(s):  
Tetsuzo Tauchi ◽  
Seiichi Okabe ◽  
Seiichiro Katagiri ◽  
Yuko Tanaka ◽  
Kaoru Tohyama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
The Self ◽  
Hedgehog Signaling Pathway ◽  
Self Renewal

scholarly journals The bHLH Repressor Deadpan Regulates the Self-renewal and Specification of Drosophila Larval Neural Stem Cells Independently of Notch

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46724 ◽  
Author(s):  
Sijun Zhu ◽  
Jill Wildonger ◽  
Suzanne Barshow ◽  
Susan Younger ◽  
Yaling Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
The Self ◽  
Self Renewal

scholarly journals Glycoprotein 130 Signaling RegulatesNotch1Expression and Activation in the Self-Renewal of Mammalian Forebrain Neural Stem Cells

2003 ◽  
Vol 23 (5) ◽  
pp. 1730-1741 ◽  
Author(s):  
Andrew Chojnacki ◽  
Takuya Shimazaki ◽  
Christopher Gregg ◽  
Gerry Weinmaster ◽  
Samuel Weiss
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
The Self ◽  
Self Renewal

scholarly journals Cross Talk between Notch and Growth Factor/Cytokine Signaling Pathways in Neural Stem Cells

2007 ◽  
Vol 27 (11) ◽  
pp. 3982-3994 ◽  
Author(s):  
Motoshi Nagao ◽  
Michiya Sugimori ◽  
Masato Nakafuku
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
The Self ◽  
Cell Surface Receptor ◽  
Cytokine Signaling ◽  
Self Renewal

ABSTRACT Precise control of proliferation and differentiation of multipotent neural stem cells (NSCs) is crucial for proper development of the nervous system. Although signaling through the cell surface receptor Notch has been implicated in many aspects of neural development, its role in NSCs remains elusive. Here we examined how the Notch pathway cross talks with signaling for growth factors and cytokines in controlling the self-renewal and differentiation of NSCs. Both Notch and growth factors were required for active proliferation of NSCs, but each of these signals was sufficient and independent of the other to inhibit differentiation of neurons and glia. Moreover, Notch signals could support the clonal self-renewing growth of NSCs in the absence of growth factors. This growth factor-independent action of Notch involved the regulation of the cell cycle and cell-cell interactions. During differentiation of NSCs, Notch signals promoted the generation of astrocytes in collaboration with ciliary neurotrophic factor and growth factors. Their cooperative actions were likely through synergistic phosphorylation of signal transducer and activator of transcription 3 on tyrosine at position 705 and serine at position 727. Our data suggest that distinct intracellular signaling pathways operate downstream of Notch for the self-renewal of NSCs and stimulation of astrogenesis.

scholarly journals Interplay between FGF2 and BMP controls the self-renewal, dormancy and differentiation of rat neural stem cells

Development ◽  
2011 ◽  
Vol 138 (12) ◽  
pp. e1-e1 ◽  
Author(s):  
Y. Sun ◽  
J. Hu ◽  
L. Zhou ◽  
S. M. Pollard ◽  
A. Smith
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
The Self ◽  
Self Renewal

CHEMICAL GENETICS REVEALS A COMPLEX FUNCTIONAL GROUND STATEOF NEURAL STEM CELLS

2008 ◽  
Vol 31 (4) ◽  
pp. 7
Author(s):  
Phedias Diamandis ◽  
Jan Wildenhain ◽  
Ian D Clarke ◽  
Adrian G Sacher ◽  
Jeremy Graham ◽  
...  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Stem Cells ◽  
Brain Cancer ◽  
Neurological Diseases ◽  
Mammalian Brain ◽  
Candidate Gene Approach ◽  
Self Renewal ◽  
Chemical Genetic

The identification of self-renewing and multipotent neural stem cells (NSCs) in the mammalian brain holds promise for the treatment of neurological diseases and has yielded newinsight into brain cancer. However, the complete repertoire of signaling pathways that governs the proliferation and self-renewal of NSCs, which we refer to as the ‘ground state’, remains largely uncharacterized. Although the candidate gene approach has uncovered vital pathways in NSC biology, so far only a few highly studied pathways have been investigated. Based on the intimate relationship between NSC self-renewal and neurosphere proliferation,we undertook a chemical genetic screen for inhibitors of neurosphere proliferation in order to probe the operational circuitry of the NSC. The screen recovered small molecules known to affect neurotransmission pathways previously thought to operate primarily in the mature central nervous system; these compounds also had potent inhibitory effects on cultures enriched for brain cancer stem cells. These results suggest that clinically approved neuromodulators may remodel the mature central nervous system and find application in the treatment of brain cancer. (colour figure available in PDF version)

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