Lnc-NA inhibits proliferation and metastasis in endometrioid endometrial carcinoma through regulation of NR4A1

J Cell Mol Med. 2019 Jul;23(7):4699-4710. doi: 10.1111/jcmm.14345. Epub 2019 May 3.


Endometrioid endometrial carcinoma (EEC) is the most common gynaecologic malignancy worldwide. Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, particularly cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in EEC have not been extensively studied. Here, we describe the discovery of Lnc-NA from the promoter of the transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) gene. The role and function of Lnc-NA in EEC remain unknown. In this study, we used quantitative real-time polymerase chain reactions to confirm that Lnc-NA expression was down-regulated in 30 EEC cases (90%) and in EEC cell lines compared with that in the paired adjacent tissues and normal endometrial cells. In vitro experiments further demonstrated that overexpressing Lnc-NA decreased EEC cell proliferation, migration and invasion and promoted apoptosis via inactivation of the apoptosis signalling pathway. Moreover, the results show that Lnc-NA expression was positively correlated with NR4A1. Furthermore, Lnc-NA regulated NR4A1 expression and activated the apoptosis signalling pathway to inhibit tumour progression. In summary, our results demonstrate that the Lnc-NA-NR4A1 axis could be a useful tumour suppressor and a promising therapeutic target for EEC.

Keywords: Lnc-NA; NR4A1; endometrial carcinoma; migration and invasion; proliferation and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Endometrioid / genetics*
  • Carcinoma, Endometrioid / pathology*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Biological
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
  • Phenotype
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction


  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • RNA, Long Noncoding