Dataset Information

MiR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22.

ABSTRACT: Charcot-Marie Tooth disease type 1A (CMT1A), the major type of CMT, is caused by duplication of peripheral myelin protein 22 (PMP22) gene whose overexpression causes structural and functional abnormalities in myelination. We investigated whether miRNA-mediated regulation of PMP22 expression could reduce the expression level of PMP22, thereby alleviating the demyelinating neuropathic phenotype of CMT1A. We found that several miRNAs were down-regulated in C22 mouse, a CMT1A mouse model. Among them, miR-381 could target 3' untranslated region (3'UTR) of PMP22 in vitro based on Western botting and quantitative Real Time-PCR (qRT-PCR) results. In vivo efficacy of miR-381 was assessed by administration of LV-miR-381, an miR-381 expressing lentiviral vector, into the sciatic nerve of C22 mice by a single injection at postnatal day 6 (p6). Administration of LV-miR-381 reduced expression level of PMP22 along with elevated level of miR-381 in the sciatic nerve. Rotarod performance analysis revealed that locomotor coordination of LV-miR-381 administered C22 mice was significantly enhanced from 8 weeks post administration. Electrophysiologically, increased motor nerve conduction velocity was observed in treated mice. Histologically, toluidine blue staining and electron microscopy revealed that structural abnormalities of myelination were improved in sciatic nerves of LV-miR-381 treated mice. Therefore, delivery of miR-381 ameliorated the phenotype of peripheral neuropathy in CMT1A mouse model by down-regulating PMP22 expression. These data suggest that miRNA can be used as a potent therapeutic strategy to control diseases with copy number variations such as CMT1A.

SUBMITTER: Lee JS

PROVIDER: S-EPMC6526106 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

miR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22.

Lee Ji-Su JS Kwak Geon G Kim Hye Jin HJ Park Hwan-Tae HT Choi Byung-Ok BO Hong Young Bin YB

Experimental neurobiology 20190430 2

Charcot-Marie Tooth disease type 1A (CMT1A), the major type of CMT, is caused by duplication of peripheral myelin protein 22 (<i>PMP22</i>) gene whose overexpression causes structural and functional abnormalities in myelination. We investigated whether miRNA-mediated regulation of PMP22 expression could reduce the expression level of PMP22, thereby alleviating the demyelinating neuropathic phenotype of CMT1A. We found that several miRNAs were down-regulated in C22 mouse, a CMT1A mouse model. Amo ...[more]

PMID: 31138995

Similar Datasets

Project description:BACKGROUND:microRNA-381 is dysregulated in a variety of cancers. However, its clinical significance in pediatric acute myeloid leukemia (AML) is still unclear. The purpose of this study was to detect the expression level of miR-381 in pediatric AML patients and to explore its potential clinical significance. METHODS:The levels of miR-381 in bone marrow and serum of 102 pediatric AML patients were measured by quantitative real-time polymorperase chain reaction (qRT-PCR). The diagnostic value of serum miR-381 in pediatric AML patients was evaluated by the receiver operating characteristic (ROC) curve. A Chi square test was used to analyze the relationship between serum miR-381 and the clinical characteristics of patients. Cox regression analysis and Kaplan-Meier evaluated the prognostic value of serum miR-381 in patients. Finally, the proliferation of the cells was analyzed by the CCK-8 assay. RESULTS:Compared with healthy controls, the levels of miR-381 in serum and bone marrow of pediatric AML patients were significantly decreased (P?<?0.001). ROC curve showed that miR-381 could distinguish pediatric AML cases from normal controls. At the same time, the downregulation of miR-381 was associated with M7 in the French-American-British (FAB) classifications and unfavorable cytogenetic risks (P?<?0.05). Low serum miR-381 levels were associated with poor overall survival of pediatric AML (log-rank test, P?=?0.011) and poor relapse-free survival (log-rank test, P?=?0.004). Cox regression analysis confirmed that reduced serum miR-381 was an independent predictor of poor prognosis in AML (HR?=?3.794, 95% CI 1.3633-10.559, P?=?0.011). In addition, low expression of miR-381 significantly reduced the proliferation of cells (P?<?0.05). CONCLUSION:All experimental results confirm that miR-381 has reduced bone marrow and serum expression in pediatric AML, and low levels of serum miR-381 have certain diagnostic and prognostic value in pediatric AML and may be a potential therapeutic target for AML.

Dataset Information

MiR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22.

Publications

miR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure