Circular RNA ciRS-7 Maintains Metastatic Phenotypes as a ceRNA of miR-1299 to Target MMPs

Abstract

Abstract Circular RNA ciRS-7 has been reported to act as a competing endogenous RNA (ceRNA) of the miRNA miR-7, resulting in reduced miR-7 activity and increased miR-7–targeted transcripts. However, it is unknown if ciRS-7 harbors other miRNAs with regulatory roles in triple-negative breast cancer (TNBC). The present study determined that the expression of ciRS-7 in TNBC clinical specimens and representative cells is significantly higher than other breast cancer subtypes. Functionally, downregulation of ciRS-7 inhibited cell migration and invasion of TNBC cells. Knockdown of ciRS-7 expression also inhibited the liver and lung metastasis of TNBC cells in vivo. Mechanistic studies revealed that ciRS-7 contains 20 miR-1299–binding sites and functions as a ceRNA of miR-1299 in TNBC cells. High expression of ciRS-7 maintains the high migration and invasion properties of TNBC cells by acting as a ceRNA of miR-1299 to enhance the expression of matrix metalloproteinases family members (MMP). Implications: Circular RNA ciRS-7 is highly expressed in TNBC tumor specimens and cells, and its downregulation inhibits cell migration and invasion of TNBC cells in vitro and in vivo. In addition, ciRS-7 functions as a ceRNA of miR-1299 to enhance the expression of MMPs, which maintains the high migration and invasion properties of TNBC cells. Mol Cancer Res; 16(11); 1665–75. ©2018 AACR.