Lineage-dependent role of miR-410-3p as oncomiR in gonadotroph and corticotroph pituitary adenomas or tumor suppressor miR in somatotroph adenomas via MAPK, PTEN/AKT, and STAT3 signaling pathways

Endocrine. 2019 Sep;65(3):646-655. doi: 10.1007/s12020-019-01960-7. Epub 2019 Jun 4.

Abstract

Purpose: miR-410-3p plays opposite roles in different cancers and may act as an oncomiR or tumor suppressor miR. The purpose of this study was to assess the role of miR-410-3p in somatotroph, gonadotroph, and corticotroph pituitary adenomas.

Methods: Tissue samples were obtained from 75 patients with pituitary adenoma. miR-410-3p expression was assessed using qRT-PCR performed on RNA isolated from fresh frozen samples. In vitro experiments were performed on cell lines derived from somatotroph (GH3), gonadotroph (RC-4B/C), and corticotroph (AtT-20) pituitary tumors. Cells were transfected with synthetic mimic of miR-410-3p or non-targeting scrambled-miR control. Subsequently, proliferation assays and transwell invasion assays were performed. The expression of cyclin D1, E1, and B1 in cells after transfection was determined using qRT-PCR. The activation of MAPK, PTEN/AKT and STAT3 signaling pathways were assessed using western blot.

Results: We have found that the level of expression of miR-410-3p differs in particular types of pituitary adenomas. miR-410-3p significantly upregulates proliferation and invasiveness of RC-4B/C and AtT-20 cells, while inhibiting GH3 cells. We observed that the levels of cyclin B1 upon transfection with miR-410-3p mimic were increased in RC-4B/C and AtT-20, yet decreased in GH3 cells. We have shown that miR-410-3p promoted the activation of MAPK, PTEN/AKT, and STAT3 signaling pathways in RC-4B/C and AtT-20 cells, but suppressed their activity in GH3 cells.

Conclusions: miR-410-3p acts as an oncomiR in gonadotroph and corticotroph adenoma cells, while as a tumor suppressor miR in somatotroph adenoma cells.

Keywords: Invasiveness; MicroRNA; PTEN; Pituitary adenoma; Proliferation; miR-410-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ACTH-Secreting Pituitary Adenoma / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclins / biosynthesis
  • Cyclins / genetics
  • Gonadotropins / metabolism*
  • Growth Hormone-Secreting Pituitary Adenoma / genetics*
  • Growth Hormone-Secreting Pituitary Adenoma / metabolism
  • Humans
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinases / genetics
  • Neoplasm Invasiveness / genetics
  • Oncogene Protein v-akt / genetics
  • PTEN Phosphohydrolase / genetics
  • Pituitary Neoplasms / genetics*
  • Pituitary Neoplasms / metabolism
  • STAT3 Transcription Factor / genetics
  • Signal Transduction / genetics*

Substances

  • Cyclins
  • Gonadotropins
  • MIRN410 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Oncogene Protein v-akt
  • Mitogen-Activated Protein Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human