MicroRNA‑20a promotes the proliferation and cell cycle of human osteosarcoma cells by suppressing early growth response 2 expression

Mol Med Rep. 2015 Oct;12(4):4989-94. doi: 10.3892/mmr.2015.4098. Epub 2015 Jul 20.

Abstract

MicroRNAs (miRNAs) are crucial in cancer development. However, the underlying mechanisms of miRNAs in osteosarcoma (OS) remain largely uncharacterized. The present study investigated the role of miR‑20a in OS cell proliferation. It was determined that miR‑20a expression is markedly upregulated in OS tissues and cells compared with the matched adjacent normal tissues and h‑FOB human osteoblast cell lines. Ectopic expression of miR‑20a promoted the proliferation and anchorage‑independent growth of OS cells, whereas inhibition of miR‑20a reduced this effect. Bioinformatics analysis further revealed early growth response 2 (EGR2), as a potential target of miR‑20a. Data from luciferase reporter assays showed that miR‑20a directly binds to the 3'‑untranslated region (3'‑UTR) of EGR2 mRNA and represses expression at the transcriptional and translational levels. In functional assays, miR‑20a promoted OS cell proliferation and the cell cycle, which could be suppressed by an inhibitor of miR‑20a. In conclusion, the data provide compelling evidence that miR‑20a functions as an onco‑miRNA, which is important in promoting cell proliferation in OS, and its oncogenic effect is mediated primarily through direct suppression of EGR2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Early Growth Response Protein 2 / antagonists & inhibitors
  • Early Growth Response Protein 2 / genetics*
  • Early Growth Response Protein 2 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Molecular Sequence Data
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Osteoblasts / metabolism*
  • Osteoblasts / pathology
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction

Substances

  • 3' Untranslated Regions
  • CCND1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • MIRN20a microRNA, human
  • MicroRNAs
  • Oligonucleotides
  • RNA, Small Interfering
  • Cyclin D1
  • Luciferases