Hsa_circ_0061140 Knockdown Reverses FOXM1-Mediated Cell Growth and Metastasis in Ovarian Cancer through miR-370 Sponge Activity

Abstract

Circular RNAs (circRNAs) are a class of noncoding RNAs that regulate gene expression at the posttranscriptional level. The specific functions of circRNAs in ovarian cancer are yet to be established. Previous sequencing analyses have revealed an abnormal expression of hsa_circ_0061140 in ovarian cancer. The main aim of the present study is to establish the specific role of hsa_circ_0061140 in ovarian cancer. circRNA expression in ovarian cancer cells was detected via real-time qPCR. The effects on specific cellular characteristics (proliferation, migration, and the EMT) and subcellular localization of hsa_circ_0061140 were assessed via RNA fluorescence in situ hybridization, knockdown, and luciferase reporter assays in the SKOV3 and A2780 cell lines. Tumorigenesis was induced in nude mice to assess the effects of hsa_circ_0061140 on ovarian cancer growth in vivo. Our results showed that hsa_circ_0061140 was upregulated in ovarian cancer cell lines. Knockdown of hsa_circ_0061140 suppressed cell proliferation and migration, both in vivo and in vitro, by inhibiting FOXM1 expression through sponging miR-370. Overexpression of FOXM1 or suppression of miR-370 rescued hsa_circ_0061140 silencing-induced inhibition of cell proliferation, migration, and the EMT. The associations among hsa_circ_0061140, miR-370, and FOXM1 were confirmed via bioinformatic prediction and fluorescein reporter experiments. Thus, hsa_circ_0061140 appeared to function as a competing endogenous RNA of miR-370 that promoted cell growth and metastasis in ovarian cancer through regulation of the miR-370/FOXM1 pathway mediating EMT.