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Int. J. Mol. Sci. 2014, 15(9), 15845-15857; https://doi.org/10.3390/ijms150915845

Targeted Suppression of Chaperone-Mediated Autophagy by miR-320a Promotes α-Synuclein Aggregation

Department of Neurosurgery, the Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China
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Received: 10 June 2014 / Revised: 30 July 2014 / Accepted: 8 August 2014 / Published: 9 September 2014
(This article belongs to the Section Biochemistry)
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Abstract

Chaperone-mediated autophagy (CMA) is involved in wild-type α-synuclein degradation in Parkinson’s disease (PD), and LAMP2A and Hsc 70 have recently been indicated to be deregulated by microRNAs. To recognize the regularory role of miR-320a in CMA and the possible role in α-synuclein degradation, in the present study, we examined the targeting and regulating role of miR-320 in Hsc 70 expression. We first constructed an α-synuclein-overexpressed human neuroblastoma cell line, SH-SY5Y-Syn(+), stably over-expressing wild-type α-synuclein and sensitive to an autophagy inhibitor, which exerted no effect on the expression of LAMP2A and Hsc 70. Then we evaluated the influence on the CMA by miR-320a in the SH-SY5Y-Syn(+) cells. It was shown that miR-320a mimics transfection of specifically targeted Hsc 70 and reduced its expression at both mRNA and protein levels, however, the other key CMA molecule, LAMP2A was not regulated by miR-320a. Further, the reduced Hsc 70 attenuated the α-synuclein degradation in the SH-SY5Y-Syn(+) cells, and induced a significantly high level of α-synuclein accumulation. In conclusion, we demonstrate that miR-320a specifically targeted the 3' UTR of Hsc 70, decreased Hsc 70 expression at both protein and mRNA levels in α-synuclein-over-expressed SH-SY5Y cells, and resulted in significant α-synuclein intracellular accumulation. These results imply that miR-320a might be implicated in the α-synuclein aggravation in PD. View Full-Text
Keywords: miR-320a; α-synuclein aggregation; Hsc 70; chaperone-mediated autophagy; Parkinson disease miR-320a; α-synuclein aggregation; Hsc 70; chaperone-mediated autophagy; Parkinson disease
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Li, G.; Yang, H.; Zhu, D.; Huang, H.; Liu, G.; Lun, P. Targeted Suppression of Chaperone-Mediated Autophagy by miR-320a Promotes α-Synuclein Aggregation. Int. J. Mol. Sci. 2014, 15, 15845-15857.

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