H19 Functions as a Competing Endogenous RNA to Regulate EMT by Sponging miR-130a-3p in Glioma

Cell Physiol Biochem. 2018;50(1):233-245. doi: 10.1159/000494002. Epub 2018 Oct 3.

Abstract

Background/aims: Glioma is one of the most devasting tumors and confers dismal prognosis. Long noncoding RNAs(lncRNAs) have emerged as important regulators in various tumors including glioma. A classic lncRNA-H19, which is found to be highly expressed in human glioma tissues and cell lines, and is associated with tumor progression thus predicating clinical outcomes in glioma patients. However, the overall biological functions and their mechanism of H19 in glioma are not fully understood.

Methods: Firstly, we analyzed H19 alterations in different grades of glioma tissues through an analysis of 5 sequencing datasets and qRT-PCR was performed to confirm the results. Next, we evaluated the effect of H19 on glioma cells migration, invasion and EMT process. Luciferase assays and RIP assays were employed to figure out the correlation of H19 and SOX4.

Results: H19 was overexpressed in glioma tissues. Down-regulation of H19 led to the inhibition of migration, invasion and EMT process with a reduction in N-cadherin and Vimentin. H19 and SOX4 are both direct target of miR-130a-3p. H19 could compete with SOX4 via sponging miR-130a-3p.

Conclusion: Taken together, these results provide a possible function of H19 as an oncogene in glioma tissues and provide a potential new therapeutic strategy for human glioma.

Keywords: Epithelial-to-mesenchymal transition; Glioma; H19.

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology*
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition / genetics
  • Glioma / drug therapy
  • Glioma / genetics
  • Glioma / mortality
  • Glioma / pathology*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism
  • Vimentin / metabolism

Substances

  • Cadherins
  • H19 long non-coding RNA
  • MIRN130 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • SOX4 protein, human
  • SOXC Transcription Factors
  • Vimentin