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miR-454-3p Is an Exosomal Biomarker and Functions as a Tumor Suppressor in Glioma

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机构: [1]Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China [2]Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China. [3]Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China [4]Department of Endocrinology, The First People's Hospital of Changzhou, Changzhou, Jiangsu, China.
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Glioma is the most common type of primary malignant brain tumor in adults. Our previous work discovered that plasma miR-454-3p may have some advantages in glioma prognosis, but the clinical significance and the regulatory mechanism of miR-454-3p in glioma have not been systematically investigated, especially regarding the relationship between circulating and tissue miR-454-3p. The expression level of miR-454-3p in glioma serum and tissues was analyzed through quantitative real-time PCR (qRT-PCR). Cell-Counting Kit 8 (CCK-8), wound healing, transwell invasion, apoptosis, and immunofluorescence assays were used to assess the role of miR-454-3p in glioma cancer cells. ATG12 was selected as the target gene of miR-454-3p by bioinformatic analysis. The relationship between ATG12 and miR-454-3p was further validated by luciferase reporter assays and Western blot analysis. miR-454-3p was significantly downregulated in tumor tissues, while it was remarkably upregulated in exosomes from the same patients with glioma. The area under curve (AUC) of exosomal miR-454-3p for glioma diagnosis was 0.8663. The exosomal miR-454-3p was prominently lower in the postoperative serums than that in the preoperative serums. High miR-454-3p expression in exosomes or low miR-454-3p expression in tissue was associated with poor prognosis. Restored expression of miR-454-3p suppressed cell proliferation, migration, invasion, and autophagy in glioma. ATG12 was validated as a direct target of miR-454-3p. The overexpression of ATG12 could partially reverse the effects induced by miR-454-3p suppression. Our data indicate that miR-454-3p may serve as an exosomal biomarker and may be developed into a novel treatment for glioma.

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出版当年[2018]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
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出版当年[2017]版:
Q1 ONCOLOGY
最新[2023]版:
Q1 ONCOLOGY

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第一作者机构: [1]Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China [2]Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
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通讯机构: [*1]Third Affiliated Hospital of Soochow University, #185 Juqian Road, Changzhou, Jiangsu 213003, China [*2]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, #1055 Sanxiang Road, Jiangsu, China
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