LncRNA FLVCR1-AS1 mediates miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in ovarian cancer

J Exp Clin Cancer Res. 2019 Aug 14;38(1):356. doi: 10.1186/s13046-019-1356-z.

Abstract

Background: Long noncoding RNAs (lncRNAs) have been reported to be associated with the proliferation of several cancer cells. The aim of this study was to investigate the role of FLVCR1-AS1 in ovarian serous cancer (OSC).

Methods: FLVCR1-AS1 expression was determined in human OSC tissues, serums and cell lines. The role of FLVCR1-AS1 knockdown or overexpression on OSC cell growth, migration, invasion, apoptosis and epithelial to mesenchymal transition (EMT) were evaluated in vitro using CCK8, colony formation assay, wound healing assay, transwell assay and western blot assay. Besides, luciferase reporter assays were performed to identify interactions among FLVCR1-AS1 and its target genes. Moreover, the in vivo effects were investigated using immunocompromised NSG female mice.

Results: In this study, FLVCR1-AS1 expression was upregulated in OSC tissues, serums, and cells. Knockdown FLVCR1-AS1 decreased cell growth, migration, invasion, and EMT, as well as increased apoptosis in OSC cells, whereas, overexpression of FLVCR1-AS1 increased cell proliferation, migration, invasion, and EMT, and decreased apoptosis of OSC cells. Besides, FLVCR1-AS1 directly bound to miR-513 and downregulated its expression. Moreover, FLVCR1-AS1 reversed the effect of miR-513 on the OSC cell growth, which might be associated with the role of YAP1. Furthermore, in terms of mechanism, FLVCR1-AS1 promoted EMT in OSC cells. Finally, mice models further confirmed that knockdown FLVCR1-AS1 distinctly suppressed cell growth and EMT in vivo.

Conclusion: Taken together, FLVCR1-AS1 mediated miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in OSC cells.

Keywords: EMT; FLVCR1-AS1; LncRNA; Ovarian serous cancer; YAP1; miR-513.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis / genetics
  • Biomarkers, Tumor
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Models, Animal
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Membrane Transport Proteins / genetics*
  • Mice
  • MicroRNAs / genetics*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • Receptors, Virus / genetics*
  • Signal Transduction*
  • Transcription Factors / metabolism*
  • Xenograft Model Antitumor Assays
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • FLVCR1 protein, human
  • MIRN513A1 microRNA, human
  • Membrane Transport Proteins
  • MicroRNAs
  • RNA, Long Noncoding
  • Receptors, Virus
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human