Article

CAMTA1 is a novel tumour suppressor regulated by miR-9/9* in glioblastoma stem cells.

Biochemistry Center Regensburg (BZR), University of Regensburg, Regensburg, Germany.
The EMBO Journal (impact factor: 9.2). 08/2011; 30(20):4309-22. DOI:10.1038/emboj.2011.301
Source: PubMed

ABSTRACT Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133(+) cell populations. We find that miR-9, miR-9(*) (referred to as miR-9/9(*)), miR-17 and miR-106b are highly abundant in CD133(+) cells. Furthermore, inhibition of miR-9/9(*) or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9(*) and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy.

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Keywords

anti-proliferative cardiac hormone natriuretic peptide
 
Calmodulin-binding transcription activator 1
 
CAMTA1
 
CAMTA1 expression
 
cancer initiating cells
 
cancer recurrence
 
fundamental roles
 
gene regulation
 
glioblastoma
 
glioblastoma therapy
 
inhibition
 
miR-17 target
 
miRNAs
 
neurosphere formation
 
NPPA
 
NPPA expression correlate
 
nude mice
 
patient survival
 
putative transcription factor