miR-339-5p inhibits migration and invasion in ovarian cancer cell lines by targeting NACC1 and BCL6

Tumour Biol. 2016 Apr;37(4):5203-11. doi: 10.1007/s13277-015-4390-2. Epub 2015 Nov 9.

Abstract

This study aimed to explore the role of miR-339-5p in ovarian cancer. The expression of miR-339-5p in seven ovarian cancer cell lines (Hey, SKOV3, OVCAR5, SKOV3-IP, A2780, CAOV3, and OVCA433) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The miR-339-5p mimic and inhibitor were used to regulate its expression. Migration, invasion, and proliferation were examined. A bioinformatics analysis was used to predict targets, and a dual-luciferase reporter system was applied for validation, along with Western blot verification. Additionally, the association of miR-339-5p and its target genes with ovarian cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. OVCAR5 and SKOV3 had the highest and lowest miR-339-5p expression, respectively. Inhibition of miR-339-5p expression increased the migration and invasion of OVCAR5 cells, while in SKOV3 cells, upregulated miR-339-5p attenuated the migration and invasion ability. Modulation of miR-339-5p had no effect on proliferation. The genes nucleus accumbens associated 1(BEN and BTB (POZ) domain containing) (NACC1) and B cell lymphoma-6 (bcl6) were validated to be targets of miR-339-5p. Clinically, patients with a high expression of NACC1 had a high risk in the survival analysis. miR-339-5p inhibits migration and invasion in ovarian cancer by targeting NACC1 and BCL6. miR-339-5p may be a biomarker of metastasis in ovarian cancer; NACC1 had a predictive value for ovarian cancer progression.

Keywords: Invasion; Migration; Ovarian cancer; miR-339-5p.

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Pregnancy-Associated Plasma Protein-A / genetics
  • Protein Tyrosine Phosphatases / genetics
  • Proto-Oncogene Proteins c-bcl-6 / biosynthesis*
  • Repressor Proteins / biosynthesis*
  • Repressor Proteins / genetics

Substances

  • BCL6 protein, human
  • Cell Cycle Proteins
  • MIRN339 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • NACC1 protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins
  • PTP4A1 protein, human
  • Protein Tyrosine Phosphatases
  • Pregnancy-Associated Plasma Protein-A
  • PAPPA protein, human