Long non-coding RNA LINC00467 drives hepatocellular carcinoma progression via inhibiting NR4A3

J Cell Mol Med. 2020 Apr;24(7):3822-3836. doi: 10.1111/jcmm.14942. Epub 2020 Mar 3.


Hepatocellular carcinoma (HCC) is a main cause of cancer-related deaths globally. Long non-coding RNAs (lncRNAs) play important roles in diverse cancers. Our previous microarray-based lncRNA profiling showed that LINC00467 was highly expressed in HCC. Here, we further explored the expression, role and functional mechanism of lncRNA LINC00467 in HCC. Our findings revealed that LINC00467 was up-regulated in HCC tissues and HCC cell lines. Increased expression of LINC00467 was positively associated with tumour size and vascular invasion. In vitro functional experiments revealed that LINC00467 accelerated HCC cell proliferation, cell cycle progression and migration and reduced HCC cell apoptosis. In vivo functional assays revealed that LINC00467 drove HCC xenograft growth and HCC cell proliferation and repressed HCC cell apoptosis in vivo. Moreover, LINC00467 inhibited NR4A3 post-transcriptionally via interacting with NR4A3 mRNA to form double-stranded RNA, which was further degraded by Dicer. The expression of NR4A3 was inversely associated with LINC00467 in HCC tissues. Functional rescue assays found that restore of NR4A3 expression blocked the oncogenic roles of LINC00467 in HCC. Taken together, our results demonstrated that lncRNA LINC00467 was a novel highly expressed and oncogenic lncRNA in HCC via inhibiting NR4A3. Targeting LINC00467 or enhancing NR4A3 may be potential therapeutic strategies against HCC.

Keywords: LINC00467; NR4A3; hepatocellular carcinoma; long non-coding RNA; oncogene.

MeSH terms

  • Aged
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics*
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Receptors, Steroid / genetics*
  • Receptors, Thyroid Hormone / genetics*


  • DNA-Binding Proteins
  • NR4A3 protein, human
  • RNA, Long Noncoding
  • Receptors, Steroid
  • Receptors, Thyroid Hormone