title: MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression.
abstract: Previous studies have suggested that microRNAs (miRNAs) play an important role in regulating neural stem cell (NSC) proliferation and differentiation. However, the precise role of miRNAs in NSC remains largely unexplored. In this study, we showed that miR-378 can target Tailless (TLX), a critical regulator of NSC, to regulate NSC proliferation and differentiation. By bioinformatic algorithms, miR-378 was found to have a predicted target site in the 3'-untranslated region of TLX, which was verified by a dual-luciferase reporter assay. The expression of miR-378 was increased during NSC differentiation and inversely correlated with TLX expression. qPCR and Western blot analysis also showed that miR-378 negatively regulated TLX mRNA and protein expression in neural stem cells (NSCs). Intriguingly, overexpression of miR-378 increased NSC differentiation and reduced NSC proliferation, whereas suppression of miR-378 led to decreased NSC differentiation and increased NSC proliferation. Moreover, the downstream targets of TLX, including p21, PTEN and Wnt/β-catenin were also found to be regulated by miR-378. Additionally, overexpression of TLX rescued the NSC proliferation deficiency induced by miR-378 overexpression and abolished miR-378-promoted NSC differentiation. Taken together, our data suggest that miR-378 is a novel miRNA that regulates NSC proliferation and differentiation via targeting TLX. Therefore, manipulating miR-378 in NSCs could be a novel strategy to develop novel interventions for the treatment of relevant neurological disorders.
authors.affiliation: Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China; Department of Rehabilitation, Xi'an Children's Hospital, Xi'an 710003, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Huang
authors.affiliation: The 3rd Department of Infectious Diseases, Xi'an Children's Hospital, Xi'an 710003, China.
authors.forename: Xiaoguai
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Psychology and Psychiatry, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. Electronic address: yapwangyy@163.com.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D006801:Humans; D007053:Ice; D066298:In Vitro Techniques; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000502:physiology*; D058953:Neural Stem Cells / Q000166:cytology*; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*
chemical_list: D007053:Ice; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; C088601:NR2E1 protein, human; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear
keywords: Cell differentiation; Cell proliferation; Neural stem cells; TLX; miR-378