Regulation of laryngeal squamous cell cancer progression by the lncRNA H19/miR-148a-3p/DNMT1 axis

Oncotarget. 2016 Mar 8;7(10):11553-66. doi: 10.18632/oncotarget.7270.

Abstract

Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer. The regulation of LSCC progression by long non-coding RNA (lncRNA) was not well understood. In this study, we reported that the lncRNA H19 was upregulated in LSCC. The expression levels of H19 were inversely correlated with the survival rate of LSCC patients. Knockdown of H19 expression inhibited LSCC cell migration, invasion and proliferation. We identified microRNA miR-148a-3p as an inhibitory target for H19. Overexpression of miR-148a-3p reduced LSCC migration, invasion and proliferation cell, while inhibition of miR-148a-3p did the opposite. The inhibition of LSCC progression induced by H19 knockdown required the activity of miR-148a-3p. We also identified DNA methyltransferase enzyme DNMT1 as a target of miR-148a-3p. Cellular DNA methylation levels were inhibited by both miR-148a-3p overexpression and H19 knockdown. In summary, our study demonstrated that the lncRNA H19 promoted LSCC progression via miR-148a-3p and DNMT1.

Keywords: DNMT1; laryngeal squamous cell cancer; lncRNA H19; miR-148a-3p.

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • DNA (Cytosine-5-)-Methyltransferase 1 / genetics
  • DNA (Cytosine-5-)-Methyltransferase 1 / metabolism*
  • DNA Methylation
  • Disease Progression
  • Female
  • HEK293 Cells
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Laryngeal Neoplasms / genetics
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Squamous Cell Carcinoma of Head and Neck
  • Survival Analysis
  • Transfection
  • Up-Regulation

Substances

  • H19 long non-coding RNA
  • MIRN148 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human