Regulation of NEAT1/miR-214-3p on the growth, migration and invasion of endometrial carcinoma cells

Arch Gynecol Obstet. 2017 Jun;295(6):1469-1475. doi: 10.1007/s00404-017-4365-1. Epub 2017 Apr 26.

Abstract

Objective: To investigate the function and mechanism of lnc NEAT1 in regulating the growth, migration and invasion of endometrial carcinoma (EC) cells.

Materials and methods: NEAT1 and miR-214-3p levels were measured by qRT-PCR. The protein levels of HMGA1, β-catenin, c-myc and MMP9 were evaluated by Western blot. The effects of NEAT1, HMGA1, miR-214-3p on the viability, migration and invasion of HEC-1A cells were accessed by WST-1 assay and transwell migration/invasion assay. The effect of miR-214-3p on Wnt signaling activity was tested by luciferase reporter assay.

Results: NEAT1, HMGA1 and β-catenin were significantly upregulated in EC tissues, and miR-214-3p was significantly downregulated. NEAT1 promoted the growth, migration and invasion of HEC-1A cells, and mRNA level of Wnt/β-catenin downstream genes c-myc and MMP9. In addition, HMGA1 upregualted the protein and mRNA levels of Wnt/β-catenin downstream genes c-myc and MMP9, and could improve cell viability, and increase numbers of migration and invasion of HEC-1A cells. miR-214-3p overexpression inhibited the proliferation, migration and invasion of HEC-1A cells, while NEAT1 overexpression reversed these effects. miR-214-3p overexpression inhibited the activity of Wnt/β-catenin pathway, while NEAT1 overexpression reversed this effect. Then, si-HMGA1 reduced the activity of Wnt/β-catenin pathway. Moreover, we found NEAT1 and HMGA1 bound to miR-214-3p by luciferase reporter assay, and NEAT1 and HMGA1 expression were negatively correlated with miR-214-3p.

Conclusion: NEAT1 regulates HMGA1 via miR-214-3p to regulate Wnt/β-catenin pathway, thus promotes the growth, migration and invasion of HEC-1A cells.

Keywords: Endometrial carcinoma; HMGA1; MiR-214-3p; NEAT1; Wnt/β-catenin pathway; c-Myc.

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • MicroRNAs / metabolism
  • MicroRNAs / physiology
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Wnt Signaling Pathway
  • beta Catenin

Substances

  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • beta Catenin
  • MMP9 protein, human
  • Matrix Metalloproteinase 9