The Potential Regulatory Mechanisms of miR-196a in Huntington's Disease through Bioinformatic Analyses

PLoS One. 2015 Sep 16;10(9):e0137637. doi: 10.1371/journal.pone.0137637. eCollection 2015.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Computational Biology / methods*
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Huntington Disease / genetics*
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Mice
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Neurites / metabolism
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Phenotype

Substances

  • Biomarkers
  • MIRN196 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by Ministry of Science and Technology (MOST 102-2628-B-006-010-MY3 and MOST 103-2320-B-006 -010) and, in part, the Ministry of Education, Taiwan, R.O.C. The Aim for the Top University Project to the National Cheng Kung University (NCKU). Computational analyses and data mining were done using the system provided by the Bioinformatics Core at National Cheng Kung University, supported by a Ministry of Science and Technology grant (MOST 97-3122-B-006 -011-).