MicroRNA-130b promotes cell proliferation and invasion by inhibiting peroxisome proliferator-activated receptor-γ in human glioma cells

Int J Mol Med. 2016 Jun;37(6):1587-93. doi: 10.3892/ijmm.2016.2580. Epub 2016 Apr 27.

Abstract

MicroRNA-130b (miR-130b) is a novel tumor-related miRNA that has been found to be involved in several biological processes. However, there is limited evidence regarding the role of miR-130b in the tumorigenesis of human gliomas. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were used to quantify miR-130b expression levels in human glioma tissues and glioma cell lines (U251, U87, SNB19 and LN229). The expression level of miR-130b was found to be markedly higher in human glioma tissues than in non‑neoplastic brain specimens. Specifically, higher expression levels of miR‑130b were observed in the glioma cell lines, compared with those in normal human astrocytes (NHA). We also confirmed that miR‑130b interacted with the 3'-untranslated region of peroxisome proliferator‑activated receptor-γ (PPAR‑γ), which negatively affected the protein levels of E-cadherin. Furthermore, its effects on cell proliferation and invasion were examined using CCK8, colony formation, cell cycle and Transwell assays. We found that the upregulation of miR-130b induced cell proliferation, decreased the percentage of cells in the G0/G1 phase and enhanced the invasiveness of U251 glioma cells whereas the downregulation of miR-130b exerted opposing effects. Moreover, it was demonstrated that the downregulation of miR‑130b in U251 glioma cells restored the expression of PPAR-γ and E-cadherin, and inhibited the expression of β-catenin. Notably, PPAR-γ knockdown abolished the inhibitory effect of miR-130b inhibitor on the proliferation and invasivness of U251 cells. Taken together, these findings suggest that miR‑130b promotes the proliferation and invasion of U251 glioma cells by inhibiting PPAR-γ.

MeSH terms

  • 3' Untranslated Regions
  • Antigens, CD
  • Astrocytoma / genetics*
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Base Sequence
  • Binding Sites
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • G1 Phase Cell Cycle Checkpoints
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • 3' Untranslated Regions
  • Antigens, CD
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • MIRN130 microRNA, human
  • MicroRNAs
  • PPAR gamma
  • RNA, Small Interfering
  • beta Catenin