title: Regulatory roles of miRNA in the human neural stem cell transformation to glioma stem cells.
abstract: To investigate the expressional alternation of microRNAs (miRNA) during the malignant transformation and development of human glioma, we measured miRNA expression profile as well as mRNA expression profile in normal human neural stem cells (hNSCs) and human glioma stem cells (hGSCs). We found 116 miRNA up-regulated and 62 miRNA down-regulated in GSCs. On the other hand, we identified 1,372 mRNA down-regulated, and 1,501 mRNA up-regulated in GSCs compared to those in NSCs. We then analyzed the pathways and the predicted target genes of the miRNAs which differ significantly in expression between GSCs and NSCs using the statistical enrichment methods. These target mRNAs are involved in many cancer-related signaling pathways, such as cell cycle, axon guidance, glioma development, adhesion junction, MAPK and Wnt signaling. Furthermore, we obtained the differently expressed miRNA-target relationships according to the θ value which is used to calculate the regulation extent of miRNA-target and using the databases of miRanda, Targetscans and Pictar. Among the top 10 miRNA-target relationships, hsa-miR-198 and its potential targeted gene DCX and NNAT were selected for validation, and NNAT was found to be the direct target of miR-198. Finally, the functional roles of miR-155-5p and miR-124-3p whose expressions altered significantly between GSCs and NSCs were addressed. Our results provide new clues for the potential mechanisms involved in the origin and development of glioma. Clinically, the altered miRNAs may serve as potential targets and diagnostic tools for novel therapeutic strategies of glioblastoma.
authors: Department of Neurosurgery, Navy General Hospital PLA, Beijing, 100048, China.
authors: Shuang
authors: S
authors: Liu
authors: Feng
authors: F
authors: Yin
authors: Jianning
authors: J
authors: Zhang
authors: Max S
authors: MS
authors: Wicha
authors: Alfred E
authors: AE
authors: Chang
authors: Wenhong
authors: W
authors: Fan
authors: Ling
authors: L
authors: Chen
authors: Ming
authors: M
authors: Fan
authors: Qiao
authors: Q
authors: Li
mesh_terms: D002471:Cell Transformation, Neoplastic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C509207:MIRN124 microRNA, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: HUMAN GLIOMA STEM CELLS; HUMAN NEURAL STEM CELLS; MICROARRAY; REGULATORY NETWORK; microRNA