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. Lentivi...
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doaj-3d46560e40a74da5baf5db8cd019398b2020-11-24T21:50:46ZengWileyCancer Medicine2045-76342019-08-018104782479110.1002/cam4.2350Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5pLingling Tong0Yu Ao1Hejia Zhang2Kun Wang3Yunyun Wang4Qingjie Ma5Department of Obstetrics and Gynecology China‐Japan Union Hospital of Jilin University Changchun ChinaDepartment of Pediatric Intensive Care Unit (PICU) The First Hospital of Jilin University Changchun ChinaDepartment of Ultrasonography China‐Japan Union Hospital of Jilin University Changchun ChinaDepartment of Obstetrics and Gynecology China‐Japan Union Hospital of Jilin University Changchun ChinaDepartment of Anesthesiology China‐Japan Union Hospital of Jilin University Changchun ChinaDepartment of Nuclear Medicine China‐Japan Union Hospital of Jilin University Changchun ChinaAbstract 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.https://doi.org/10.1002/cam4.2350epithelial ovarian cancerhsa‐miR‐155‐5plncRNAmiRNANORAD |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lingling Tong Yu Ao Hejia Zhang Kun Wang Yunyun Wang Qingjie Ma |
spellingShingle |
Lingling Tong Yu Ao Hejia Zhang Kun Wang Yunyun Wang Qingjie Ma Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p Cancer Medicine epithelial ovarian cancer hsa‐miR‐155‐5p lncRNA miRNA NORAD |
author_facet |
Lingling Tong Yu Ao Hejia Zhang Kun Wang Yunyun Wang Qingjie Ma |
author_sort |
Lingling Tong |
title |
Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p |
title_short |
Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p |
title_full |
Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p |
title_fullStr |
Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p |
title_full_unstemmed |
Long noncoding RNA NORAD is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with miR‐155‐5p |
title_sort |
long noncoding rna norad is upregulated in epithelial ovarian cancer and its downregulation suppressed cancer cell functions by competing with mir‐155‐5p |
publisher |
Wiley |
series |
Cancer Medicine |
issn |
2045-7634 |
publishDate |
2019-08-01 |
description |
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. |
topic |
epithelial ovarian cancer hsa‐miR‐155‐5p lncRNA miRNA NORAD |
url |
https://doi.org/10.1002/cam4.2350 |
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