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miR-202水平降低通过靶向Sp1促进口腔癌发展。

Reduced miR-202 levels enhanced oral cancer development via targeting Sp1.

作者信息

Zhao Jia, Ding Deguang, Zhao Ge

机构信息

Special Clinic, Jinan Stomatology Hospital, Jinan, Shandong 250001, P.R. China.

Department of Stomatology, Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250001, P.R. China.

出版信息

Exp Ther Med. 2019 Jul;18(1):489-496. doi: 10.3892/etm.2019.7603. Epub 2019 May 23.

DOI:10.3892/etm.2019.7603
PMID:31258685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6566103/
Abstract

The current study aimed to evaluate the possible role of microRNA (miR)-202 in the development of oral cancer. First, miR-202 levels were found to be decreased in the serum and tissues of oral cancer patients compared with healthy controls. Receiver operating characteristic analysis was carried out to explore the diagnostic value of serum miR-202 for oral cancer. Overexpression of miR-202 significantly decreased the migratory capacity of SCC-9 cells, while inhibition of miR-202 markedly increased the migratory capacity of SCC-9 cells. Moreover, the invasive capacity was decreased in SCC-9 cells transfected with an miR-202 mimic. In addition, the invasive capacity was enhanced in SCC-9 cells transfected with an miR-202 inhibitor. A dual luciferase reporter assay showed that overexpression of miR-202 markedly suppressed the relative luciferase activity of the pmirGLO-SP1-3'untranslated region. Overexpression of miR-202 suppressed the protein level of Sp1, but inhibition of miR-202 markedly enhanced the protein expression of Sp1. Inhibition of miR-202 enhanced the phosphorylation of protein kinase B. Additionally, the correlations between the expression levels of Sp1 and miR-202 and the clinicopathological factors of oral cancer were analyzed. The results showed that patients with high expression of Sp1 and miR-202 progressed to earlier clinical stages, had deeper infiltration depths and were more prone to lymph node metastasis compared with the healthy controls. In conclusion, the current study presented novel data indicating that decreased miR-202 enhanced the progression of oral cancer via Sp1.

摘要

本研究旨在评估微小RNA(miR)-202在口腔癌发生发展中的可能作用。首先,发现与健康对照相比,口腔癌患者血清和组织中的miR-202水平降低。进行了受试者工作特征分析,以探讨血清miR-202对口腔癌的诊断价值。miR-202过表达显著降低了SCC-9细胞的迁移能力,而抑制miR-202则显著提高了SCC-9细胞的迁移能力。此外,用miR-202模拟物转染的SCC-9细胞的侵袭能力降低。另外,用miR-202抑制剂转染的SCC-9细胞的侵袭能力增强。双荧光素酶报告基因检测显示,miR-202过表达显著抑制了pmirGLO-SP1-3'非翻译区的相对荧光素酶活性。miR-202过表达抑制了Sp1的蛋白水平,但抑制miR-202则显著增强了Sp1的蛋白表达。抑制miR-202增强了蛋白激酶B的磷酸化。此外,分析了Sp1和miR-202的表达水平与口腔癌临床病理因素之间的相关性。结果显示,与健康对照相比,Sp1和miR-202高表达的患者临床分期较早,浸润深度更深,更容易发生淋巴结转移。总之,本研究提供了新的数据,表明miR-202降低通过Sp1促进口腔癌进展。

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