Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR-155-5p

Abstract

Purpose: In the present study, we evaluated the expression and function of human long noncoding RNA (lncRNA) activated by DNA damage (NORAD) in human epithelial ovarian cancer (EOC). Methods: NORAD expression was evaluated by qRT-PCR in EOC cell lines and in situ EOC clinical samples. Lentivirus-mediated NORAD downregulation was conducted in OVCAR-3 and ES-2 cells, and its effect on cancer cell proliferation, bufalin chemoresistance, cell-cycle transition in vitro, and xenotransplantation in vivo were examined, respectively. The likelihood of an lncRNA-microRNA (miRNA) signaling pathway was examined by probing the possible downstream competing target of NORAD, hsa-miR-155-5p. Moreover, hsa-miR-155-5p was knocked down in NORAD-downregulated EOC cells to functionally evaluate the correlation between NORAD and hsa-miR-155-5p in EOC. Results: We found that NORAD was substantially upregulated in both EOC cell lines and human tumors. In OVCAR-3 and ES-2 cells, lentivirus-mediated NORAD downregulation had significant anticancer effects, as it suppressed cell proliferation, decreased bufalin chemoresistance, arrested cell-cycle transition, and inhibited xenograft growth. Also, hsa-miR-155-5p was confirmed to be the competing target of NORAD in EOC, and its knockdown in OVCAR-3 and ES-2 cells reversed the NORAD downregulation-induced anticancer functions. Conclusions: NORAD is upregulated in EOC. Inhibition of NORAD, possibly through endogenously competing against hsa-miR-155-5p, can be a new tumor-suppressing strategy in EOC.