The Neuroprotective Effect of miR-196a on Neuronal Morphology through Targeting IMP3

• Main Authors: Han-InYang, 楊涵茵
• Other Authors: Shang-Hsun Yang
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/58uxq5

碩士 === 國立成功大學 === 生理學研究所 === 106 === Huntington’s disease (HD) is an inherited neurodegenerative disease leading to motor control dysfunction and cognitive deficit in patients, resulting from the neurotoxicity primarily in the central nervous system (CNS) along with altered gene expression. Previously, our research had found that overexpression of miR-196a ameliorated pathological phenotypes of HD models in vitro and in vivo and provided beneficial regulations for neuronal cytoskeleton. We now elucidate the mechanism of the neuroprotective effects of miR-196a. Bioinformatics predicts that insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3 or IMP3) is a potential target gene of miR-196a, which is involved in cytoskeleton remodeling during malignant transformation in cancers. Therefore, we hypothesize that miR-196a may improve the neuronal morphology through targeting IMP3. Here, we confirm that miR-196a inhibits the endogenous expression level of IMP3 in N2a cells by targeting the 3’UTR of IMP3 transcript. Besides, the endogenous IMP3 is suppressed in miR-196a transgenic mice. We further show that miR-196a inhibits IMP3 in N2a cells differentiated by retinoic acid and in mouse primary cortical neurons, and overexpression of IMP3 blocks the morphology protective effect of miR-196a. Additionally, the exogenous IMP3 restrains the neurite outgrowth and leads to abnormal morphology, including decreased F-actin intensity and flattened cell shape. Furthermore, in screening the expression profiling of IMP3 in the R6/2 HD mouse model, we find an ectopic expression pattern of IMP3 in their adult cortical tissues, which is distinct from the wild type mice and correlated with disease progression. These results implicate a detrimental role of elevated IMP3 in neuronal pathogenesis, and miR-196a may provide beneficial effects for neuronal morphology through targeting IMP3. In future work, we will study the role of IMP3 in the neuroprotective effect of miR-196a in HD models in vitro and in vivo. We anticipate that this study will shed light on promising treatment strategies for HD.