miR-372 inhibits p62 in head and neck squamous cell carcinoma in vitro and in vivo

Oncotarget. 2015 Mar 20;6(8):6062-75. doi: 10.18632/oncotarget.3340.

Abstract

Here we showed that exogenous miR-372 expression and knockdown of p62 (sequestosome1 or SQSTM1), both increased migration of head and neck squamous cell carcinoma (HNSCC) cells. p62 induced phase II detoxification enzyme NADPH quinone oxidoreductase 1 (NQO1), which decreased ROS levels and cell migration. Also, miR-372 decreased p62 during hypoxia, thus increasing cell migration. Levels of miR-372 and p62 inversely correlated in human HNSCC tissues. Plasma levels of miR-372 was associated with advanced tumor stage and patient mortality. Both plasma and salivary miR-372 levels were decreased after tumor resection. We conclude that miR-372 decreases p62, thus increasing ROS and motility in HNSCC cells.

Keywords: carcinoma; hypoxia; invasion; miR-372; mouth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cell Hypoxia / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • HEK293 Cells
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / administration & dosage*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis
  • Prognosis
  • RNA-Binding Proteins / antagonists & inhibitors*
  • RNA-Binding Proteins / biosynthesis
  • Reactive Oxygen Species / metabolism
  • Squamous Cell Carcinoma of Head and Neck
  • Xenograft Model Antitumor Assays

Substances

  • MIRN372 microRNA, human
  • MicroRNAs
  • P62 protein, human
  • RNA-Binding Proteins
  • Reactive Oxygen Species
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human