The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network

Fareh, Mohamed; Turchi, Laurent; Virolle, Virginie; Debruyne, David; Almairac, Fabien; Divonne, S de-la-Forest; Paquis, Philippe; Preynat‐Seauve, Olivier; Krause, Karl-Heinz; Chneiweiss, Hervé; Virolle, Thierry

doi:10.1038/cdd.2011.89

Cited by 159 publications

(139 citation statements)

References 37 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…These aberrantly expressed miRNAs play essential roles in the regulation of TIC properties as either TIC suppressors or promoters [20][21][22][23][24] . Moreover, a series of critical signalling pathways involved in the regulation of TIC properties have been uncovered with the identification of the targets of these miRNAs 19,[25][26][27][28] . Importantly, miRNAs are also demonstrated to be promising biomarkers and amenable therapeutic targets 5,19,24 .…”

mentioning

confidence: 99%

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Han

Zhao

et al. 2015

Nat Commun

View full text Add to dashboard Cite

Tumour-initiating cells (TICs) are advocated to constitute the sustaining force to maintain and renew fully established malignancy; however, the molecular mechanisms responsible for these properties are elusive. We previously demonstrated that voltage-gated calcium channel a2d1 subunit marks hepatocellular carcinoma (HCC) TICs. Here we confirm directly that a2d1 is a HCC TIC surface marker, and identify let-7c, miR-200b, miR-222 and miR-424 as suppressors of a2d1 þ HCC TICs. Interestingly, all the four miRNAs synergistically target PBX3, which is sufficient and necessary for the acquisition and maintenance of TIC properties. Moreover, PBX3 drives an essential transcriptional programme, activating the expression of genes critical for HCC TIC stemness including CACNA2D1, EpCAM, SOX2 and NOTCH3. In addition, the expression of CACNA2D1 and PBX3 mRNA is predictive of poor prognosis for HCC patients. Collectively, our study identifies an essential signalling pathway that controls the switch of HCC TIC phenotypes.

show abstract

mentioning

confidence: 99%

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Han

Zhao

et al. 2015

Nat Commun

View full text Add to dashboard Cite

show abstract

“…4 miRNA dysregulation is a common feature of neoplasia and numerous miRNAs have been characterized as oncogenes or tumor suppressors in many cancers including in glioblastoma (GBM). 3,[5][6][7][8][9][10][11] microRNA-134 (miR-134) has been implicated in the regulation of physiological and developmental processes. It was shown to promote mouse embryonic stem-cell differentiation, dendritogenesis, and stage-specific cortical development.…”

mentioning

confidence: 99%

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Zhang

Mueller

et al. 2014

Cell Death Differ

View full text Add to dashboard Cite

Receptor tyrosine kinases (RTKs) are co-deregulated in a majority of glioblastoma (GBM), the most common and most deadly brain tumor. We show that the RTKs MET, EGFR, and PDGFR regulate microRNA-134 (miR-134) in GBM. We find that miR-134 is downregulated in human tumors and cancer stem cells and that its expression inversely correlates with the activation of MET, EGFR, and PDGFR. We demonstrate that miR-134 inhibits cancer cell and stem-cell proliferation, survival, and xenograft growth, as well as cancer stem-cell self-renewal and stemness. We identify KRAS and STAT5B as targets of miR-134, and establish molecular and functional links between RTKs, miR-134, KRAS/STAT5B and malignancy in vitro and in vivo. We show that miR-134 induction is required for the anti-tumor effects of RTK inhibitors. We also uncover the molecular pathways through which RTKs regulate miR-134 expression and demonstrate the involvement of MAPK signaling and the KLF4 transcription factor. We therefore identify miR-134 as a novel RTK-regulated tumor-suppressive hub that mediates RTK and RTK-inhibitor effects on GBM malignancy by controlling KRAS and STAT5B. Cell Death and Differentiation (2014) 21, 720-734; doi:10.1038/cdd.2013; published online 17 January 2014 microRNAs (miRNAs) regulate a wide variety of physiological and pathological processes. 1-3 miRNAs modulate protein expression by binding to the 3 0 untranslated region (3 0 UTR) of target mRNA and promoting RNA degradation and/or inhibiting translation. Single miRNAs can regulate multiple molecules, highlighting a powerful mechanism for the regulation of redundant and cross-talking signal transduction pathways. 4 miRNA dysregulation is a common feature of neoplasia and numerous miRNAs have been characterized as oncogenes or tumor suppressors in many cancers including in glioblastoma (GBM). 3,[5][6][7][8][9][10][11] microRNA-134 (miR-134) has been implicated in the regulation of physiological and developmental processes. It was shown to promote mouse embryonic stem-cell differentiation, dendritogenesis, and stage-specific cortical development. 12-17 miR-134 is downregulated by SIRT1 and involved in synaptic plasticity and memory formation. 18 miR-134 expression is regulated by MEF2 in dendritogenesis 14 and GBM. 19 GBM is the most common and most deadly primary malignant brain tumor. 20,21 The Cancer Genome Atlas and other studies have shown that aberrant expression or activation of the receptor tyrosine kinases (RTKs) EGFR, MET, and PDGFR occurs in a majority of GBM and correlates with poor prognosis. 22 Importantly, multiple RTKs are co-activated in the same GBM tumors and tumor cells. 23,24 KRAS, STAT3, and STAT5 are activated by RTKs and mediate their oncogenic effects. [25][26][27][28] The failure of current treatments for GBM is arguably due to the presence in the tumors of GBM stem cells (GSCs) that are resistant to radioand chemo-therapy and capable of maintaining and propagating the tumors. 29-31 EGFR, MET, PDGFR, and miRNAs have been implicated in the regulation of GSC f...

show abstract

“…Up-regulation of miR-302/367 has been reported in glioblastoma multiforme. It is shown that this miR cluster is rapidly and strongly induced in glioma-initiating cells (Fareh et al, 2012). In addition, miR-302 is reported to be enriched in human leukaemia cell lines (Yu et al, 2006), large B cell lymphoma (Lawrie et al, 2009).…”

Section: B Amentioning

confidence: 99%

Role of stem cell proteins and microRNAs in embryogenesis and germ cell cancer

Eini¹,

Dorssers²,

Looijenga³

2013

Int. J. Dev. Biol.

View full text Add to dashboard Cite

show abstract

The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network

Cited by 159 publications

References 37 publications

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells

Multiple receptor tyrosine kinases converge on microRNA-134 to control KRAS, STAT5B, and glioblastoma

Role of stem cell proteins and microRNAs in embryogenesis and germ cell cancer

Contact Info

Product

Resources

About