CREB1 induced lncRNA HAS2-AS1 promotes epithelial ovarian cancer proliferation and invasion via the miR-466/RUNX2 axis

Biomed Pharmacother. 2019 Jul:115:108891. doi: 10.1016/j.biopha.2019.108891. Epub 2019 May 10.


Accumulating evidence has indicated the vital roles of long noncoding RNA (lncRNA) in the epithelial ovarian cancer (EOC). However, the function of lncRNA HAS2-AS1 in EOC is still unclear. This study aims to investigate the expression and role of HAS2-AS1 in EOC. In the cells and tissue of EOC, HAS2-AS1 expression was markedly up-regulated. Besides, the overexpression of HAS2-AS1 indicated the poor clinical outcome of EOC patients. Transcription factor CREB1 could bind with the promoter of HAS2-AS1 and activate its transcriptional expression. Functionally, HAS2-AS1 knockdown suppressed the proliferation, invasion and tumor growth of EOC cells in vitro and in vivo. Mechanical investigation found that HAS2-AS1 could relive the RUNX2 protein expression via sponging the miR-466, acting as miRNA sponge. In conclusion, this finding suggests the CREB1/HAS2-AS1/miR-466/RUNX2 axis in the in the EOC tumorigenesis, providing the novel insight for the molecular mechanism of EOC.

Keywords: CREB1; Epithelial ovarian cancer; HAS2-AS1; RUNX2; miR-466.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / physiopathology*
  • Neoplasms, Experimental
  • Ovarian Neoplasms / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Specific Pathogen-Free Organisms
  • Transfection


  • CREB1 protein, human
  • Core Binding Factor Alpha 1 Subunit
  • Cyclic AMP Response Element-Binding Protein
  • MIRN466 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RUNX2 protein, human
  • long noncoding RNA HAS2-AS1, human