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

Lingling Tong,Kun Wang,Yunyun Wang,Hejia Zhang,Yu Ao,Qingjie Ma

doi:10.1002/cam4.2350

Lingling Tong, Kun Wang + Show 4 more

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https://doi.org/10.1002/cam4.2350

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Abstract

PurposeIn 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).MethodsNORAD 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.ResultsWe 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.ConclusionsNORAD 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.

Highlights

Epithelial ovarian cancer (EOC) is one of the most lethal forms of gynecologic malignancy in women of age 40 or older.[1-3]
We evaluated the effect of NORAD downregulation on EOC cell‐cycle transition in vitro
Mounting evidence has demonstrated that epigenetic regulation of long noncoding RNA (lncRNA) plays important roles in human cancer progression, and may hold the key to developing novel molecular target for cancer treatment.[10-12]

Summary

| INTRODUCTION

Epithelial ovarian cancer (EOC) is one of the most lethal forms of gynecologic malignancy in women of age 40 or older.[1-3]. LncRNAs have been identified to play important roles, at both transcriptional and posttranscriptional levels, in modulating gene expressions and regulating a variety of physiological processes in eukaryotic cells.[7-9]. A very recent study showed that NORAD upregulated and modulated cancer cell proliferation and invasion in one of the most common gynecologic cancers, cervical cancer.[16]. It is still unknown whether NORAD may be dysregulated in another common type of gynecologic cancers, EOC, or whether NORAD may be actively participating in the functional regulation of cancer development in EOC.

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| DISCUSSION