microRNA‐130a suppresses breast cancer cell migration and invasion by targeting FOSL1 and upregulating ZO‐1

• Published in: Journal of cellular biochemistry 2018-06, Vol.119 (6), p.4945-4956
• Main Authors: Chen, Xiaowei, Zhao, Min, Huang, Jin, Li, Yuhuang, Wang, Shunqing, Harrington, Christina A., Qian, David Z., Sun, Xiao‐Xin, Dai, Mu‐Shui
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Breast cancer; Cancer; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement; DNA microarrays; Ectopic expression; Female; FOSL1; Gene expression; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Immunoprecipitation; Invasiveness; Kinases; Metastases; MicroRNAs - biosynthesis; MicroRNAs - genetics; miRNA; miR‐130a; Neoplasm Invasiveness; Proto-Oncogene Proteins c-fos - biosynthesis; Proto-Oncogene Proteins c-fos - genetics; Ribonucleic acid; RNA; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; tight junction; Transfection; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Up-Regulation; Zonula Occludens-1 Protein - biosynthesis; Zonula Occludens-1 Protein - genetics; ZO‐1
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26739

FOSL1 is frequently overexpressed in multiple types of human cancers including invasive breast cancers and implicated in cancer invasion and metastasis. However, how FOSL1 is overexpressed in cancers remains to be elucidated. Several microRNAs (miRNAs) have been shown to target FOSL1 and are downregulated in human cancers. Here, we report that miR‐130a is a novel FOSL1 targeting miRNA. Using gene expression microarray analysis, we found that FOSL1 is among the most up‐regulated genes in cells transfected with miR‐130a inhibitors. Transient transfection‐immunoblot, RNA‐immunoprecipitation, and luciferase reporter assays revealed that miR‐130a directly targets FOSL1 mRNA at its 3′‐UTR. Overexpression of miR‐130a significantly reduced the levels of FOSL1 in invasive breast cancer MDA‐MB‐231 and Hs578T cell lines and suppresses their migration and invasion. This inhibition can be rescued by ectopic expression of miR‐130a‐resistant FOSL1. Interestingly, we show that overexpression of miR‐130a increased the levels of tight‐junction protein ZO‐1 while inhibition of miR‐130a reduced the levels of ZO‐1. We further show that miR‐130a expression is significantly reduced in cancer tissues from triple‐negative breast cancer (TNBC) patients, correlating significantly with the upregulation of FOSL1 expression, compared to non‐TNBC tissues. Together, our results reveal that miR‐130a directly targets FOSL1 and suppresses the inhibition of ZO‐1, thus inhibiting cancer cell migration and invasion, in TNBCs. In this manuscript, we identified: (1) FosL1 is a novel miR‐130a target; (2) miR‐130a expression is reduced, correlating with FOSL1 upregulation, in triple negative breast cancers; and (3) the miR‐130a‐FosL1 pathway regulates breast cancer cell migration and invasion.