MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK-Snai2 pathway
MicroRNA-181a suppresses salivary adenoid cystic carcinoma metastasis by targeting MAPK-Snai2 pathway
复制标题
MicroRNA-181a 通过靶向 MAPK-Snai2 通路抑制唾液腺腺样囊性癌转移。
DOI：
10.1016/j.bbagen.2013.07.028
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发表时间：
2013-11-01
影响因子：
3
通讯作者：
Wang, Anxun
中科院分区：
文献类型：
--
作者：
He, Qianting;Zhou, Xiaofeng;Wang, Anxun
背景：到目前为止，microrna及其在涎腺样囊性癌（SACC）的发生和增殖中的作用是有限的。本研究的目的是确定miR-181a及其在SACC转移中的机制。方法：首先采用微阵列技术和定量RT-PCR技术研究不同转移潜能的SACC配对细胞系的microRNA谱和miR-181a。然后研究miR-181a对SACC转移潜能的影响。利用荧光素酶报告基因检测研究MiR-181a靶基因和Snai2启动子活性。Western blot检测MAPK-Snai2通路相关蛋白水平。结果：在一对SACC细胞系中鉴定出一组不受调控的microrna（包括miR-181a）。功能分析表明，miR-181a在体外抑制SACC细胞的迁移、侵袭和增殖，在体内抑制肿瘤生长和肺转移。通过荧光素酶报告基因检测证实了miR-181a直接靶向MAP2K1、MAPK1和Snai2。MiR-181a mimic抑制SACC细胞中MAP2K1、MAPK1和Snai2的表达。MAP2K1或MAPK1 siRNA抑制Snai2基因启动子活性，降低Snai2的表达和SACC细胞的转移潜能。结论：我们的研究结果表明miR-181a在SACC的转移中起重要作用，可能作为SACC的新的治疗靶点。MiR-181a调控MAPK-Snai2通路既通过直接顺调控机制，也通过间接反调控机制。一般意义：据我们所知，这是第一个揭示miR-181a失调通过调节MAPIC-Snai2通路介导SACC转移的研究。(C) 2013 Elsevier B.V.版权所有
Background: To date microRNAs and their contribution to the onset and propagation of salivary adenoid cystic carcinoma (SACC) are limited. The objective of this study was to identify miR-181a and its mechanism in the metastasis of SACC.Methods: At first microarray and quantitative RT-PCR were used to investigate microRNA profiles and miR-181a in paired SACC cell lines with different metastatic potential. Then the effect of miR-181a on metastatic potential of SACC was investigated. MiR-181a target genes and Snai2 promoter activity were investigated using luciferase reporter gene assays. Western blot was used to detect MAPK-Snai2 pathway-related protein level.Results: A panel of deregulated microRNAs (including miR-181a) was identified in paired of SACC cell lines. Functional analysis indicated that miR-181a inhibited SACC cell migration, invasion and proliferation in vitro, and it suppressed tumor growth and lung metastasis in vivo. Direct targeting of miR-181a to MAP2K1, MAPK1 and Snai2 was confirmed by luciferase reporter gene assays. MiR-181a mimic inhibited the expression of MAP2K1, MAPK1 and Snai2 in SACC cells. MAP2K1 or MAPK1 siRNA suppressed Snai2 gene promoter activity and reduced Snai2 expression and the metastatic potential of SACC cells.Conclusions: Our results indicate that miR-181a plays an important role in the metastasis of SACC, and may serve as a novel therapeutic target for SACC. MiR-181a regulates the MAPK-Snai2 pathway both through direct cisregulatory mechanism and through indirect trans-regulatory mechanism.General significance: To our knowledge, this is the first study revealing that miR-181a deregulation mediated the metastasis of SACC by regulating MAPIC-Snai2 pathway. (C) 2013 Elsevier B.V. All rights reserved.