MiR-124 suppresses tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma

Molecular Cancer

Research

Hao Ran Huang¹  Xia Xu¹  Xiang Ping Li¹  Fei Peng Zhao¹  Xiong Liu¹  Juan Lu¹  Huai Hong Chen¹  Fan Wang¹  Lu Wang¹  Xiao Hong Peng¹  Shao Xiong Lin²  Bao Zhang³ 

[1] Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China;Department of Otorhinolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China;Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Shantou University Medical College, 515041, Shantou, Guangdong, China;School of Public Health and Tropical Medicine, Southern Medical University, 510515, Guangzhou, China;

关键词: MicroRNA-124;    Tumor growth;    Metastasis;    Nasopharyngeal carcinoma;    Foxq1;   

DOI  :  10.1186/1476-4598-13-186

 received in 2014-04-05, accepted in 2014-08-01,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundThe molecular mechanisms underlying dysregulation of microRNAs have been documented in nasopharyngeal carcinoma (NPC). Our previous study demonstrated that plasma miR-124 was down-regulated in NPC using microarray analysis and quantitative PCR validation. Though growing studies showed that down-regulated miR-124 was closely related to tumourigenesis in various types of cancers, the role of miR-124 in NPC remains largely unknown.MethodsThe expression level of miR-124 was evaluated in NPC cell lines and patient specimens using quantitative reverse transcription-PCR (Real-time qPCR). The clinicopathological significance of the resultant data was later analyzed. Then, we explored the role of miR-124 in NPC tumorigenesis by in vitro and in vivo experiments. Homo sapiens forkhead box Q1 (Foxq1) was confirmed as a novel direct target gene of miR-124 by the dual-luciferase assay and western bolt.ResultsWe found that miR-124 was commonly down-regulated in NPC specimens and NPC cell lines. The expression of miR-124 was inversely correlation with clinical stages and marked on T stages. Then, the ectopic expression of miR-124 dramatically inhibited cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth and metastasis in vivo. Furthermore, we identified Foxq1 as a novel direct target of miR-124. Functional studies showed that knockdown of Foxq1 inhibited cell growth, migration and invasion, whereas Foxq1 overexpression partially rescued the suppressive effect of miR-124 in NPC. In clinical specimens, Foxq1 was commonly up-regulated in NPC, and the level increased with clinical stages and T stages. Additionally, the level of Foxq1 was inversely correlated with miR-124.ConclusionsOur results demonstrate that miR-124 functions as a tumor-suppressive microRNA in NPC, and that its suppressive effects are mediated chiefly by repressing Foxq1 expression. MiR-124 could serve as an independent biomarker to identify patients with different clinical characteristics. Therefore, our findings provide valuable clues toward the understanding the of mechanisms of NPC pathogenesis and provide an opportunity to develop new effective clinical therapies in the future.

【 授权许可】

Unknown   
© Peng et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.