MiR-125b orchestrates cell proliferation, differentiation and migration in neural stem/progenitor cells by targeting Nestin

• Published in: BMC neuroscience Vol. 13; no. 1; p. 116
• Main Authors: Cui, Yi, Xiao, Zhifeng, Han, Jin, Sun, Jie, Ding, Wenyong, Zhao, Yannan, Chen, Bing, Li, Xiaoran, Dai, Jianwu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 28.09.2012; BioMed Central; BMC
• Subjects: 3' Untranslated regions; Analysis; Analysis of Variance; Animals; Animals, Newborn; Binding sites; Bromodeoxyuridine - metabolism; Cell differentiation; Cell Differentiation - drug effects; Cell Differentiation - physiology; Cell migration; Cell Movement - drug effects; Cell Movement - physiology; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Data processing; Differentiation; Hippocampus - cytology; Intermediate Filament Proteins - metabolism; MicroRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - metabolism; Migration; MiR-125b; miRNA; mRNA; Mutation; Mutation - genetics; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nervous system; Nestin; Neural stem cells; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neural stem/progenitor cells; Neurons; Physiological aspects; Rats; Rats, Sprague-Dawley; RNA, Small Interfering - pharmacology; siRNA; Spinal cord; Statistical analysis; Stem cells; Studies; Time Factors; Transfection; Canada; China; Beijing China
• ISSN: 1471-2202; 1471-2202
• DOI: 10.1186/1471-2202-13-116

The emerging concept is that microRNAs (miRNAs) play a central role in controlling stem cell self-renewal and fate determination by regulating the expression of stem cell regulators. miR-125b, one of neuronal miRNAs, recently was found to be necessary for neural differentiation of neural stem/progenitor cells (NS/PCs). However, the other specific biological role of miR-125b in NS/PCs is little known. We used rat NS/PCs as a model system to study the role of miR-125b in governing the behavior of NS/PCs. We report here the transfection of exogenous miR-125b inhibited proliferation of NS/PCs but promoted differentiation and migration. Whereas anti-miR-125b had the opposite effect. Similar results were observed when Nestin was knocked down by siRNA. Subsequently, we demonstrated that Nestin was a direct functional target of miR-125b. MiR-125b downregulates the expression of luciferase through Nestin 3'untranslated region (3'-UTR), and the regulation was abolished by mutations in the miR-125b binding site. MiR-125b targeted the 3'-UTR of Nestin and reduced the abundance of Nestin at both mRNA and protein levels. The results provided new insight into the function by which miR-125b modulates NS/PCs proliferation, differentiation and migration. The data also indicated the regulatory role of miR-125b in NS/PCs might through the suppression of Nestin expression.