Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p. (28th June 2019)

• Record Type: Journal Article
• Authors: Tong, Lingling; Ao, Yu; Zhang, Hejia; Wang, Kun; Wang, Yunyun; Ma, Qingjie
• Is Part Of: Cancer medicine. Volume 8:Number 10(2019:Aug.)
• Page Start: 4782
• Page End: 4791
• Publication Date: 2019-06-28
• Subjects: epithelial ovarian cancer -- hsa‐miR‐155‐5p -- lncRNA -- miRNA -- NORAD; 616.994005
• DOI: 10.1002/cam4.2350
• Languages: English
• ISSNs: 2045-7634

Abstract

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. Abstract : 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.