MicroRNA-543 promotes cell invasion and impedes apoptosis in pituitary adenoma via activating the Wnt/β-catenin pathway by negative regulation of Smad7

Biosci Biotechnol Biochem. 2019 Jun;83(6):1035-1044. doi: 10.1080/09168451.2019.1591260. Epub 2019 Apr 11.

Abstract

Pituitary adenomas (PA) are commonly occurring benign neoplasms. Identification of molecular pathway resulting in pituitary tumorigenesis remains challenges in endocrine oncology. The present study was conducted with aim of investigating the role of microRNA-543 (miR-543) in PA development. Up-regulated miR-543 and downregulated Smad7 were observed in PA tissues. Afterwards, the specific mechanism of miR-543 and Smad7 in PA were determined with the use of ectopic expression, depletion and reporter assay experiments. Smad7 was confirmed as a target gene of miR-543. HP75 cells treated with overexpressed miR-543 exhibited increased cell proliferation, migration and invasion, while decreased cell apoptosis as well as expression of Cleaved caspase-3 and Cleaved caspase-8 were observed. Suppression of miR-543 contributed to an opposite trend to the above findings. Based on the findings, the inhibition of miR-543 was found to play a tumor suppressive role in PA through the down-regulation of Wnt/β-catenin pathway by negatively regulating Smad7.

Keywords: MicroRNA-543; Wnt/β-catenin pathway; apoptosis; invasion; mothers against decapentaplegic homolog 7; pituitary adenoma.

MeSH terms

  • Adenoma / metabolism*
  • Adenoma / pathology*
  • Adult
  • Apoptosis / genetics*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Humans
  • Male
  • MicroRNAs / physiology*
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Pituitary Neoplasms / metabolism*
  • Pituitary Neoplasms / pathology*
  • Smad7 Protein / metabolism*
  • Up-Regulation
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • MIRN453 microRNA, human
  • MicroRNAs
  • SMAD7 protein, human
  • Smad7 Protein
  • beta Catenin
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8