Abstract 5328: MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting the ERK/Slug pathway.

Abstract

Abstract MicroRNA deregulation plays a major role in the initiation and progression of many cancers. The objective of this study is to evaluate the role of miR-181a in the metastasis of salivary adenoid cystic carcinoma (SACC). We identified a panel of differentially expressed microRNAs in two pairs SACC cell lines with different metastatic potential using microarrays. Among these differentially expressed microRNAs, the down-regulation of miR-181a was further validated by quantitative RT-PCR. Functional analysis indicated that miR-181a inhibits SACC cell migration, invasion and proliferation in vitro and in vivo. Ectopic transfection of miR-181a inhibited the expression of NGF, VEGF, TGFβ2, ERK1/2, pERK1/2 and Slug in SACC-LM cells which had higher expression of these genes compared to SACC-83 cells; while inverse results were found in miR-181a LNA transfected SACC-83 cells. The direct targeting of miR-181a to the Slug and ERK2 mRNAs were confirmed by luciferase reporter gene assays. SiRNA-mediated knockdown of Slug, ERK2 led to reduced cell migration and invasion of SACC, and knockdown of ERK2 suppresses the expression of Slug. Taken together, these results suggest that microRNA deregulation (i.e., down-regulation of miR-181a) contributes to the metastasis of SACC. MiR-181a-mediated suppression of SACC metastasis may be achieved in part by directly targeting Slug and ERK2 and regulating ERK/Slug pathway. Citation Format: Qianting He, Xiaofeng Zhou, Su Li, Zhujian Chen, Dan Chen, Yuchen Cai, Zhonghua Liu, Tingting Zhao, Anxun Wang. MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting the ERK/Slug pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5328. doi:10.1158/1538-7445.AM2013-5328