The Biological Role of the Long Non-coding RNA LINK-A in Ovarian Carcinoma

Anticancer Res. 2020 Dec;40(12):6677-6684. doi: 10.21873/anticanres.14691.

Abstract

Aim: To analyze the biological role of the long non-coding RNA LINK-A.

Materials and methods: An 850-bp segment from the second exon of LINK-A was removed using the CRISPR/Cas9 system in OVCA433 ovarian serous carcinoma cells. Spheroid formation, migration, invasion, proliferation, matrix metalloproteinase (MMP) activity and expression of cell-signaling proteins were assessed in vitro.

Results: OVCA433 cells with LINK-A deletion were more invasive (p=0.0008) but had reduced migration and MMP9 secretion compared to controls (p=0.003 and p=0.005, respectively). LINK-A deletion did not affect proliferation but induced phosphorylation of extracellular signal-regulated kinase (10-fold; p=0.005). LINK-A knock out additionally reduced spheroid formation.

Conclusion: Added to our previous data from analysis of clinical specimens, LINK-A is likely to be a tumor suppressor.

Keywords: CRISPR/Cas9; LINK-A; high-grade serous carcinoma; in vitro.; long non-coding RNA; tumorigenesis.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Invasiveness
  • Nucleic Acid Conformation
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / genetics*
  • Phosphorylation
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology

Substances

  • RNA, Long Noncoding
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinases