Microrna-124 targets flotillin-1 to regulate proliferation and migration in breast cancer

Molecular Cancer

Research

Xiaoming Xie¹  Xinhua Xie¹  Jie Gao¹  Yanan Kong¹  Jiaoli Guo¹  Hailing Tang¹  Xiaoti Lin¹  Xiangdong Xu²  Linjing Yuan³  Dong Wang⁴  Bo Wang⁴  Laisheng Li⁴  Min Liu⁴  Jinmei Luo⁵  Shaoyan Xi⁶ 

[1] Department of Breast Oncology, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People’s Republic of China;Department of Breast Oncology, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, People’s Republic of China;Department of Gynecology, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People’s Republic of China;Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, 510080, Guangzhou, People’s Republic of China;Department of Medical Intensive Care Unit, Third Affiliated Hospital of Sun Yat-sen University, 510630, Guangzhou, People’s Republic of China;Department of Pathology, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People’s Republic of China;

关键词: Breast cancer;    miR-124;    FLOT1;    Proliferation;    Migration;   

DOI  :  10.1186/1476-4598-12-163

 received in 2013-08-12, accepted in 2013-12-11,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) have been documented as playing important roles in cancer development. In this study, we investigated the role of miR-124 in breast cancer and clarified the regulation of flotillin-1 (FLOT1) by miR-124.MethodsThe expression levels of miR-124 were examined in breast cancer cell lines and patient specimens using quantitative reverse transcription-PCR. The clinicopathological significance of the resultant data was later analyzed. Next, we explored the function of miR-124 to determine its potential roles on cancer cell growth and migration in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-124, and the results were validated in cell lines and patient specimens.ResultsWe found that miR-124 expression was significantly downregulated in breast cancer cell lines and patient specimen compared with normal cell lines and paired adjacent normal tissues (P < 0.0001), respectively. MiR-124 was also associated with tumor node metastasis (TNM) stage (P = 0.0007) and lymph node metastasis (P = 0.0004). In breast cancer cell lines, the ectopic expression of miR-124 inhibited cell growth and migration in vitro. Moreover, we identified the FLOT1 gene as a novel direct target of miR-124, and miR-124 ectopic expression significantly inhibited FLOT1. Luciferase assays confirmed that miR-124 could directly bind to the 3′ untranslated region of FLOT1 and suppress translation. Moreover, FLOT1 was widely upregulated, and inversely correlated with miR-124 in breast cancer tissues. Consistent with the effect of miR-124, the knockdown of FLOT1 significantly inhibited breast cancer cell growth and migration. We also observed that the rescue expression of FLOT1 partially restored the effects of miR-124.ConclusionsOur study demonstrated that miR-124 might be a tumor suppressor in breast cancer via the regulation of FLOT1. This microRNA could serve as a potential diagnostic marker and therapeutic target for breast cancer.

【 授权许可】

Unknown   
© Li et al.; licensee BioMed Central Ltd. 2013. 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/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.