Long noncoding RNA OIP5-AS1 targets Wnt-7b to affect glioma progression via modulation of miR-410

Biosci Rep. 2019 Jan 3;39(1):BSR20180395. doi: 10.1042/BSR20180395. Print 2019 Jan 31.

Abstract

The present study was undertaken to investigate the underlying mechanisms of long noncoding RNA OIP5-AS1 via regulating miR-410 to modulate Wnt-7b in the progression of glioma. To address this problem, we measured the expression of OIP5-AS1 and miR-410 in glioma tissues by qRT-PCR. Glioma U87 cells were transfected with OIP5-AS1 siRNA or miR-410 inhibitors. The targeting relationships among miR-410, OIP5-AS1 and Wnt-7b were verified by luciferase reporter assays. Western blotting was employed to determine the expression of Wnt-7b/β-catenin pathway-related proteins, while MTT, flow cytometry, Transwell assays and wound-healing assays were used to measure the biological characteristics of glioma cells. The results showed that OIP5-AS1 expression was higher and miR-410 was lower in glioma tissues. Luciferase reporter assays confirmed a targeting relationship between OIP5-AS1 and miR-410, as well as between miR-410 and Wnt-7b. Silencing OIP5-AS1 reduced cell proliferation, invasion and migration of glioma U87 cells and led to depressed expression levels of miR-410, Wnt-7b, p-β-catenin, GSK-3β-pS9, c-Myc and cyclin D1. Furthermore, down-regulation of OIP5-AS1 induced G0/G1 phase cell cycle arrest and apoptosis of glioma cells. Inhibitors of miR-410 abolished the biological effects of OIP5-AS1 siRNA in glioma cells. In vivo, OIP5-AS1 knockdown also inhibited tumor growth. Taken together, this research suggested that silencing OIP5-AS1 may specifically block the Wnt-7b/β-catenin pathway via targeted up-regulating miR-410, thereby inhibiting growth, invasion and migration while promoting apoptosis in glioma cells.

Keywords: Invasion; Long noncoding RNA; Migration; Proliferation; glioma; microRNA.

MeSH terms

  • Adult
  • Animals
  • Apoptosis / genetics
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Cycle / genetics
  • Cell Proliferation
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics
  • Glioma / metabolism
  • Glioma / pathology
  • Glioma / therapy*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Middle Aged
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway
  • Xenograft Model Antitumor Assays
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CCND1 protein, human
  • CTNNB1 protein, human
  • MIRN410 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • WNT7B protein, human
  • Wnt Proteins
  • beta Catenin
  • long noncoding RNA OIP5, human
  • Cyclin D1
  • Glycogen Synthase Kinase 3 beta