Deregulation of miR-520d-3p promotes hepatocellular carcinoma development via lncRNA MIAT regulation and EPHA2 signaling activation

Biomed Pharmacother. 2019 Jan;109:1630-1639. doi: 10.1016/j.biopha.2018.11.014. Epub 2018 Nov 16.


MicroRNA-520d-3p (miR-520d-3p) is a novel cancer-related miRNA and functions as a tumor suppressor in human cancers. However, the expression patterns and mechanisms of miR-520d-3p involved in hepatocellular carcinoma (HCC) remain rarely known. Here, we found that the expression levels of miR-520d-3p in HCC tissues and cells were significantly lower than in tumor-adjacent tissues and L02 cells. Decreased level of miR-520d-3p was relevant to poor overall survival, whereas miR-520d-3p up-regulation resulted in a marked inhibition of cell growth, migration and invasion. In addition, the long non-coding RNA, myocardial infarction associated transcript (MIAT) was up-regulated in both HCC tissues and cell lines. MIAT suppressed the expression and function of miR-520d-3p. Moreover, erythropoietin-producing hepatocellular A2 (EPHA2) was speculated and confirmed as a direct target of miR-520d-3p. We also demonstrated that MIAT may function as a sponge competitive endogenous RNA for miR-520d-3p, and thus regulate the molecular expression of EPHA2. In summary, our study has identified a novel signaling pathway through which miR-520d-3p exerts its anticarcinogenic roles and suggested that the MIAT/miR-520d-3p/EPHA2 may be a new target for HCC therapy.

Keywords: Hepatocellular carcinoma; LncRNA; MIAT; MiR-520d-3p.

MeSH terms

  • Adult
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Ephrin-A2 / biosynthesis*
  • Female
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • MicroRNAs / biosynthesis*
  • Middle Aged
  • RNA, Long Noncoding / physiology*
  • Signal Transduction / physiology


  • EphA2 receptor, human
  • Ephrin-A2
  • MIRN520 microRNA, human
  • Miat long non-coding RNA
  • MicroRNAs
  • RNA, Long Noncoding