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

作者：Laisheng Li, Jinmei Luo, Bo Wang, Dong Wang, Xinhua Xie, Linjing Yuan, Jiaoli Guo, Shaoyan Xi, Jie Gao, Xiaoti Lin, Yanan Kong, Xiangdong Xu, Hailin Tang, Xiaoming Xie, Min Liu · 发表于：Molecular Cancer · 年份：2013 · DOI：10.1186/1476-4598-12-163 · 被引用次数：115 · 研究领域：Caveolin-1 and cellular processes、Lipid metabolism and disorders、Kruppel-like factors research

BACKGROUND: MicroRNAs (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. METHODS: The 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. RESULTS: We 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 ...