LncRNA TTN-AS1 acts as sponge for miR-15b-5p to regulate FBXW7 expression in ovarian cancer

Biofactors. 2020 Jul;46(4):600-607. doi: 10.1002/biof.1622. Epub 2020 Feb 12.

Abstract

Emerging evidence showed that long noncoding RNA (lncRNA) plays crucial roles in regulating various cancer biological behaviors. Titin-antisense RNA1 (TTN-AS1) has been reported to have crucial roles in cancers but its role in ovarian cancer remains unknown. The levels of TTN-AS1, microNRA-15b-5p (miR-15b-5p), and F-box and WD repeat domain containing 7 (FBXW7) in ovarian cancer cells were measured by quantitative reverse-transcription PCR. Targets for TTN-AS1 and miR-15b-5p were predicted by bioinformatic tools, and validated by luciferase activity reporter assay. Cell proliferation, colony formation, and cell apoptosis were analyzed with cell counting kit-8 assay, colony formation assay, and flow cytometry. Correlation of TTN-AS1 and FBXW7 was analyzed at gene expression profiling interactive analysis. TTN-AS1 was found decreased expression in ovarian cancer tissues and cells. Dual-luciferase activity validated TTN-AS1 and FBXW7 shared binding site in miR-15b-5p. Functional assays showed TTN-AS1 overexpression inhibits ovarian cancer cell proliferation, colony formation but promotes apoptosis. Rescue experiments showed that knockdown of FBXW7 could partially counteracted the effects of TTN-AS1 overexpression on ovarian cancer cell behaviors. Our results indicated that the TTN-AS1/miR-15b-5p/FBXW7 axis identified in this work could help to identify treatment biomarkers for ovarian cancer.

Keywords: FBXW7; TTN-AS1; miR-15b-5p; ovarian cancer.

MeSH terms

  • Apoptosis / genetics
  • Base Pairing
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Computational Biology
  • Connectin / genetics*
  • Connectin / metabolism
  • F-Box-WD Repeat-Containing Protein 7 / antagonists & inhibitors
  • F-Box-WD Repeat-Containing Protein 7 / genetics*
  • F-Box-WD Repeat-Containing Protein 7 / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • Connectin
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • MIRN15 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • TTN protein, human
  • Luciferases