Oncotarget

Research Papers:

CPEB1 modulates differentiation of glioma stem cells via downregulation of HES1 and SIRT1 expression

Jinlong Yin, Gunwoo Park, Jeong Eun Lee, Ju Young Park, Tae-Hoon Kim, Youn-Jae Kim, Seung-Hoon Lee, Heon Yoo _, Jong Heon Kim and Jong Bae Park

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Oncotarget. 2014; 5:6756-6769. https://doi.org/10.18632/oncotarget.2250

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Abstract

Jinlong Yin1,*, Gunwoo Park1,*, Jeong Eun Lee2,3, Ju Young Park2,3, Tae-Hoon Kim1, Youn-Jae Kim1, Seung-Hoon Lee1,3, Heon Yoo1,3, Jong Heon Kim2,3 and Jong Bae Park1,3

1 Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea

2 Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea

3 Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi , Korea

* These authors contributed equally to this work

Correspondence:

Jong Bae Park, email:

Jong Heon Kim, email:

Heon Yoo, email:

Keywords: Glioma stem cell, self-renewal, differentiation, CPEB1

Received: June 26, 2014 Accepted: July 22, 2014 Published: July 23, 2014

Abstract

Glioma stemness has been recognized as the most important reason for glioma relapse and drug resistance. Differentiation of glioma stem cells (GSCs) has been implicated as a novel approach to target recurrent glioma. However, the detailed molecular mechanism involved in the differentiation of GSCs has not yet been elucidated. This study identified CPEB1 as the key modulator that induces the differentiation of GSCs at the post-transcriptional level. Gain and loss of function experiments showed that CPEB1 expression reduced sphere formation ability and the expression of stemness markers such as Nestin and Notch. To elucidate the detailed molecular mechanism underlying the action of CPEB1, we investigated the interacting ribonome of the CPEB1 complex using a Ribonomics approach. CPEB1 specifically suppressed the translation of HES1 and SIRT1 by interacting with a cytoplasmic polyadenylation element. The expression profile of CPEB1 negatively correlated with overall survival in glioma patients. Overexpression of CPEB1 decreased the number of GSCs in an orthotopically implanted glioma animal model. These results suggest that CPEB1-mediated translational control is essential for the differentiation of GSCs and provides novel therapeutic concepts for differentiation therapy.


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