在头颈肿瘤发生过程中，miR-31/96/182靶向Numb基因。

Targeting of miR-31/96/182 to the Numb gene during head and neck oncogenesis.

作者信息

Chou Chung-Hsien, Tu Hsi-Feng, Kao Shou-Yen, Chiang Chun-Yu Fan, Liu Chung-Ji, Chang Kuo-Wei, Lin Shu-Chun

机构信息

Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.

Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan.

出版信息

Head Neck. 2018 Apr;40(4):808-817. doi: 10.1002/hed.25063. Epub 2018 Jan 22.

DOI:10.1002/hed.25063

PMID:29356167

Abstract

BACKGROUND

MicroRNAs (miRNAs) play crucial roles in head and neck squamous cell carcinoma (HNSCC). This study investigates whether miR-31, miR-96, and miR-182 are involved in targeting Numb during HNSCC.

METHODS

The expression of miR-31/96/182 in tumor tissues was analyzed. Reporter assay, knockdown, expression, and oncogenic analysis were carried out in cell lines.

RESULTS

Upregulation of miR-31/96/182 was detected in tumor tissues. In addition, advanced tumors showed higher expression levels of these miRNAs. The expression of these miRNAs was upregulated after treatment with areca ingredients (P < .01 or P < .001). These miRNAs directly targeted the 3' untranslated region (UTR) sequence of the Numb gene. An increased migration and invasion of HNSCC cells was associated with the exogenous expression of miR-31/96/182 (P < .01 or P < .001), and this was reverted by expression of Numb.

CONCLUSION

This study provides new evidence demonstrating that there is frequent and concordant upregulation of miR-31, miR-96, and miR-182 during HNSCC and these miRNAs co-target Numb.

摘要

背景

微小RNA（miRNA）在头颈部鳞状细胞癌（HNSCC）中发挥关键作用。本研究调查miR-31、miR-96和miR-182在HNSCC发生过程中是否参与靶向Numb。

方法

分析肿瘤组织中miR-31/96/182的表达。在细胞系中进行报告基因检测、敲低、表达及致癌性分析。

结果

在肿瘤组织中检测到miR-31/96/182上调。此外，进展期肿瘤显示这些miRNA表达水平更高。用槟榔成分处理后，这些miRNA的表达上调（P < 0.01或P < 0.001）。这些miRNA直接靶向Numb基因的3'非翻译区（UTR）序列。HNSCC细胞迁移和侵袭增加与miR-31/96/182的外源性表达相关（P < 0.01或P < 0.001），而Numb的表达可逆转这种情况。