MiRNA-218, a new regulator of HMGB1, suppresses cell migration and invasion in non-small cell lung cancer

Acta Biochim Biophys Sin (Shanghai). 2013 Dec;45(12):1055-61. doi: 10.1093/abbs/gmt109. Epub 2013 Nov 17.

Abstract

MicroRNAs (miRNAs) function as negative regulators of gene expression involved in cancer metastasis. The aim of this study is to investigate the potential roles of miR-218 in non-small cell lung cancer and validate its regulation mechanism. Functional studies showed that miR-218 overexpression inhibited cell migration and invasion, but had no effect on cell viability. Enhanced green fluorescent protein reporter assay, real-time polymerase chain reaction and western blot analysis confirmed that miR-218 suppressed the expression of high mobility group box-1 (HMGB1) by directly targeting its 3'-untranslated region. Accordingly, silencing of HMGB1 accorded with the effects of miR-218 on cell migration and invasion, and overexpression of HMGB1 can restore cell migration and invasion which were reduced by miR-218. In conclusion, these findings demonstrate that miR-218 functions as a tumor suppressor in lung cancer. Furthermore, miR-218 may act as a potential therapeutic biomarker for metastatic lung cancer patients.

Keywords: HMGB1; miR-218; microRNA; non-small lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HMGB1 Protein / genetics*
  • HMGB1 Protein / metabolism
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • 3' Untranslated Regions
  • HMGB1 Protein
  • MIRN218 microRNA, human
  • MicroRNAs
  • Green Fluorescent Proteins