MicroRNA-155 is a novel suppressor of ovarian cancer-initiating cells that targets CLDN1

• We isolated ovarian cancer-initiating cells from human primary ovarian tumor tissues.
• Low miRNA-155 in OCICs correlates with CLDN1 overexpression.
• We confirmed CLDN1 mRNA to be a novel target of microRNA-155.
• MiR-155 overexpression specifically inhibits OCIC proliferation and invasion.
• MiR-155 transfection decreases OCIC xenograft tumor growth.

Previous cDNA microarrays indicated that CLDN1 (claudin-1) is an important gene for ovarian cancer-initiating cell (OCIC) invasion and adhesion. Here, we show that the downregulation of miR-155 in OCICs correlates with CLDN1 overexpression and the suppression of OCIC invasion. Luciferase assays indicate that miR-155 targets CLDN1 mRNA on the 3′ UTR. CLDN1 mRNA and claudin-1 protein expression were significantly decreased in miR-155-OCICs. Proliferation assays and Transwell migration assays show that miR-155 significantly suppresses the proliferative and invasive capacity of OCICs. Furthermore, miR-155 suppresses the growth of OCIC xenograft tumors. Thus, overexpression of miR-155 may prevent tumorigenesis in human ovarian cancer through downregulation of CLDN1.