title: cAMP response element-binding protein promotes gliomagenesis by modulating the expression of oncogenic microRNA-23a.
abstract: 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.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences,  Chinese Academy of Medical Sciences and  Peking Union Medical College, Beijing 100005,  China.
authors.forename: Xiaochao
authors.initials: X
authors.lastname: Tan
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.forename: Liyuan
authors.initials: L
authors.lastname: Zhu
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Yin
authors.forename: Jizong
authors.initials: J
authors.lastname: Zhao
authors.forename: Jiangang
authors.initials: J
authors.lastname: Yuan
authors.forename: Boqin
authors.initials: B
authors.lastname: Qiang
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Peng
mesh_terms: D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C549404:MIRN204 microRNA, human; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human