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

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 <i>in vivo</i> 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).<b>Implications:</b> Circular RNA ciRS-7 is highly expressed in TNBC tumor specimens and cells, and its downregulation inhibits cell migration and invasion of TNBC cells <i>in vitro</i> and <i>in vivo</i> 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. <i>Mol Cancer Res; 16(11); 1665-75. ©2018 AACR</i>.