cAMP response element-binding protein promotes gliomagenesis by modulating the expression of oncogenic microRNA-23a.

Xiaochao Tan, Shan Wang, Liyuan Zhu, Chao Wu, Bin Yin, Jizong Zhao, Jiangang Yuan, Boqin Qiang, Xiaozhong Peng

Proceedings of the National Academy of Sciences of the United States of America 2012 Sep 25

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Gliomas are the most common and deadly type of primary brain tumor. In this study, we showed that cAMP response element-binding protein (CREB), a proto-oncogenic transcription factor that is overexpressed in gliomas, can promote gliomagenesis by modulating the expression of oncogenic microRNA-23a (mir-23a). First, we found that CREB is highly expressed in glioma tissues and cell lines. CREB is also essential for glioma cell growth and cell survival in vitro and is critical for gliomagenesis in vivo. Second, microRNA microarray, ChIP-chip, ChIP-quantitative PCR, and luciferase reporter assays showed that CREB directly binds to the regulatory sequences of mir-23a and enhance the expression of mir-23a. Moreover, mir-23a was confirmed as a functional downstream target of CREB in glioma cell growth and cell survival. Finally, using computational prediction followed by experimental confirmation, we identified PTEN, which is frequently silenced in gliomas, as a downstream target of mir-23a. Taken together, we propose that CREB promotes gliomagenesis and acts as a modulator of oncogenic mir-23a, which represses the tumor suppressor PTEN.

Citation

Xiaochao Tan, Shan Wang, Liyuan Zhu, Chao Wu, Bin Yin, Jizong Zhao, Jiangang Yuan, Boqin Qiang, Xiaozhong Peng. cAMP response element-binding protein promotes gliomagenesis by modulating the expression of oncogenic microRNA-23a. Proceedings of the National Academy of Sciences of the United States of America. 2012 Sep 25;109(39):15805-10