LncRNA NEAT1 promotes autophagy via regulating miR-204/ATG3 and enhanced cell resistance to sorafenib in hepatocellular carcinoma

J Cell Physiol. 2020 Apr;235(4):3402-3413. doi: 10.1002/jcp.29230. Epub 2019 Sep 23.


Long noncoding RNAs (lncRNAs) has been acknowledged in tumorigenesis gradually because of the great importance in different cancers. LncRNA nuclear enriched abundant transcript 1 (NEAT1) is a novel lncRNA and has been reported to promote multiple cancer progression. However, the biological roles of NEAT1 in hepatocellular carcinoma (HCC) is not cleared nowadays. In the present research, the level of NEAT1 was found to be upregulated in HCC by The Cancer Genome Atlas. In addition, NEAT1 expression is negatively correlated with the survival rate in HCC. Further investigation revealed that NEAT1 upregulation inhibited sorafenib efficacy and promoted autophagy. We found that NEAT1 could be a sponge for microRNA-204 (miR-204) and inhibits its level to upregulate ATG3 expression. In addition to the above, we demonstrated that miR-204 mimics also attenuated tumor autophagy. And rescue assays demonstrated that NEAT1 promotes HCC autophagy through modulating miR-204/ATG3 pathway. Collectively, this study first demonstrated that a novel NEAT1/miR-204/ATG3 signaling regulates HCC progression.

Keywords: HCC; NEAT1; autophagy; miRNA; sorafenib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / drug effects
  • Autophagy-Related Proteins / genetics*
  • Carcinogenesis
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Sorafenib / pharmacology
  • Ubiquitin-Conjugating Enzymes / genetics*


  • Autophagy-Related Proteins
  • MIRN204 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Sorafenib
  • Ubiquitin-Conjugating Enzymes
  • ATG3 protein, human