miR-196a Enhances Neuronal Morphology through Suppressing RANBP10 to Provide Neuroprotection in Huntington's Disease

• Published in: Theranostics 2017-01, Vol.7 (9), p.2452-2462
• Main Authors: Her, Lu-Shiun, Mao, Su-Han, Chang, Chih-Yi, Cheng, Pei-Hsun, Chang, Yu-Fan, Yang, Han-In, Chen, Chuan-Mu, Yang, Shang-Hsun
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Guanine Nucleotide Exchange Factors - antagonists & inhibitors; Huntington Disease - pathology; Mice, Transgenic; MicroRNAs - metabolism; Microtubule-Associated Proteins - antagonists & inhibitors; Neurons - cytology; Neurons - pathology; Neuroprotection; Protein Multimerization; Research Paper; Tubulin - metabolism
• ISSN: 1838-7640; 1838-7640
• DOI: 10.7150/thno.18813

MicroRNAs (miRNAs) play important roles in several neurobiological processes, including the development and progression of diseases. Previously, we identified that one specific miRNA, miR-196a, provides neuroprotective effects on Huntington's disease (HD), although the detailed mechanism is still unclear. Based on our bioinformatic analyses, we hypothesize miR-196a might offer neuroprotective functions through improving cytoskeletons of brain cells. Here, we show that miR-196a could enhance neuronal morphology, further ameliorating intracellular transport, synaptic plasticity, neuronal activity, and learning and memory abilities. Additionally, we found that miR-196a could suppress the expression of RAN binding protein 10 (RANBP10) through binding to its 3' untranslated region, and higher expression of RANBP10 exacerbates neuronal morphology and intracellular transport. Furthermore, miR-196a enhances neuronal morphology through suppressing RANBP10 and increasing the ability of β-tubulin polymerization. Most importantly, we observed higher expression of RANBP10 in the brains of HD transgenic mice, and higher expression of RANBP10 might exacerbate the pathological aggregates in HD. Taken together, we provide evidence that enhancement of neuronal morphology through RANBP10 is one of the neuroprotective mechanisms for miR-196a. Since miR-196a has also been reported in other neuronal diseases, this study might offer insights with regard to the therapeutic use of miR-196a in other neuronal diseases.