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miR-611 通过靶向 FOXN3 促进舌鳞癌细胞的增殖、迁移和侵袭。

miR-611 promotes the proliferation, migration and invasion of tongue squamous cell carcinoma cells by targeting FOXN3.

机构信息

Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.

Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.

出版信息

Oral Dis. 2019 Nov;25(8):1906-1918. doi: 10.1111/odi.13177. Epub 2019 Sep 2.

Abstract

OBJECTIVES

The function of miR-611 has not yet been reported. We aimed to investigate the effects of miR-611 on tongue squamous cell carcinoma (TSCC) and the underlying mechanism.

MATERIALS AND METHODS

The expression level of miR-611 in TSCC tissues was measured using quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Cell proliferation, migration and invasion were examined by performing CCK-8, IncuCyte and Transwell assays. Bioinformatics analyses and microarrays were used to screen for target genes, which were verified using a luciferase reporter assay, RT-qPCR and Western blotting. The xenograft model was used to assess the effects of miR-611 in vivo.

RESULTS

miR-611 was upregulated in TSCC tissues, which was significantly correlated with TNM stage and negatively associated with the overall survival of patients. In addition, upregulation of miR-611 not only potentiated the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of TSCC cells in vitro, but also promoted tumour growth in vivo. FOXN3 was identified as a candidate target gene of miR-611 and subsequently verified. Finally, miR-611 induced a malignant phenotype of TSCC, which was rescued by overexpression of FOXN3.

CONCLUSIONS

Our findings suggest that miR-611 is a novel therapeutic target for TSCC.

摘要

目的

miR-611 的功能尚未见报道。本研究旨在探讨 miR-611 对舌鳞状细胞癌(TSCC)的影响及其潜在机制。

材料与方法

采用实时定量逆转录聚合酶链反应(RT-qPCR)检测 TSCC 组织中 miR-611 的表达水平。通过 CCK-8、IncuCyte 和 Transwell 实验检测细胞增殖、迁移和侵袭能力。通过生物信息学分析和微阵列筛选靶基因,并通过荧光素酶报告基因检测、RT-qPCR 和 Western blot 进行验证。利用异种移植模型评估 miR-611 在体内的作用。

结果

miR-611 在 TSCC 组织中上调,与 TNM 分期显著相关,与患者的总生存率呈负相关。此外,miR-611 的上调不仅增强了 TSCC 细胞的体外增殖、迁移、侵袭和上皮-间充质转化(EMT)能力,而且促进了体内肿瘤生长。FOXN3 被鉴定为 miR-611 的候选靶基因,并得到进一步验证。最后,miR-611 诱导了 TSCC 的恶性表型,而过表达 FOXN3 则可挽救该表型。

结论

本研究结果表明,miR-611 是 TSCC 的一种新型治疗靶点。

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