LncRNA SNHG20 knockdown suppresses the osteosarcoma tumorigenesis through the mitochondrial apoptosis pathway by miR-139/RUNX2 axis

Biochem Biophys Res Commun. 2018 Sep 10;503(3):1927-1933. doi: 10.1016/j.bbrc.2018.07.137. Epub 2018 Jul 30.

Abstract

Increasing evidence has indicated the important roles of long noncoding RNAs (lncRNAs) in human osteosarcoma tumorigenesis. In present study, we aim to investigate the roles of lncRNA SNHG20 (small nucleolar RNA host gene 20) in osteosarcoma tumorigenesis and explore the in-depth molecular mechanism. Results showed that lncRNA SNHG20 expression was up-regulated in osteosarcoma samples and its high-expression indicated the poor prognosis. Loss-of-functional experiments indicated that SNHG20 knockdown inhibited the proliferation, invasion and induced the apoptosis of osteosarcoma cells in vitro. Specifically, SNHG20 knockdown up-regulated the expression levels of caspase-9, caspase-3 and Bax, indicating that SNHG20 knockdown accelerated the apoptosis of osteosarcoma cells via mitochondrial apoptosis pathway. Bioinformatics analysis revealed that miR-139 both targeted with the 3'-UTR of runt-related transcription factor 2 (RUNX2) and SNHG20, which was verified by luciferase reporter assay and RNA immunoprecipitation (RIP). In conclusion, our data reveals that lncRNA SNHG20/miR-139/RUNX2 axis modulates the osteosarcoma tumorigenesis and apoptosis via mitochondrial apoptosis pathway, providing a novel insight for the pathophysiological process.

Keywords: Mitochondrial apoptosis; Osteosarcoma; RUNX2; SNHG20; miR-139.

MeSH terms

  • Adolescent
  • Animals
  • Apoptosis*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Proliferation
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Tumor Cells, Cultured

Substances

  • Core Binding Factor Alpha 1 Subunit
  • MIRN139 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RUNX2 protein, human
  • long non-coding RNA SNHG20, human