title: The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses.
abstract: High throughput screening is a powerful tool to identify the potential candidate molecules involved during disease progression. However, analysis of complicated data is one of the most challenging steps on the way to obtaining useful results from this approach. Previously, we showed that a specific miRNA, miR-196a, could ameliorate the pathological phenotypes of Huntington's disease (HD) in different models, and performed high throughput screening by using the striatum of transgenic mice. In this study, we further tried to identify the potential regulatory mechanisms using different bioinformatic tools, including Database for Annotation, Visualization and Integrated Discovery (DAVID), Molecular Signatures Database (MSigDB), TargetScan and MetaCore. The results showed that miR-196a dominantly altered "ABC transporters", "RIG-I-like receptor signaling pathway", immune system", "adaptive immune system","tissue remodeling and wound repair" and "cytoskeleton remodeling". In addition, miR-196a also changed the expression of several well-defined pathways of HD, such as apoptosis and cell adhesion. Since these analyses showed the regulatory pathways are highly related to the modification of the cytoskeleton, we further confirmed that miR-196a could enhance the neurite outgrowth in neuroblastoma cells, suggesting miR-196a might provide beneficial functions through the alteration of cytoskeleton structures. Since impairment of the cytoskeleton has been reported in several neuronal diseases, this study will provide not only the potential working mechanisms of miR-196a but also insights for therapeutic strategies for use with different neuronal diseases.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Mu-Hui
authors.initials: MH
authors.lastname: Fu
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Li
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Division of Breeding and Genetics, Livestock Research Institute, Council of Agriculture, Tainan 71246, Taiwan.
authors.forename: Hsiu-Lien
authors.initials: HL
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Shaw-Jeng
authors.initials: SJ
authors.lastname: Tsai
authors.affiliation: Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Yen-Yu
authors.initials: YY
authors.lastname: Lai
authors.affiliation: Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Cheng
authors.affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Chuan-Mu
authors.initials: CM
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan; Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D016501:Neurites / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D010641:Phenotype
chemical_list: D015415:Biomarkers; C542543:MIRN196 microRNA, human; D035683:MicroRNAs