Overexpression of miR-200a suppresses epithelial-mesenchymal transition of liver cancer stem cells

Tumour Biol. 2015 Apr;36(4):2447-56. doi: 10.1007/s13277-014-2856-2. Epub 2014 Nov 22.

Abstract

Due to high incidence of invasion and intrahepatic metastasis, hepatocellular carcinoma (HCC) is one of the most aggressive tumors in the world, which is also associated with the acquisition of epithelial-mesenchymal transition (EMT). Increasing evidence suggests that cancer cells with EMT traits share many biological characteristics with cancer stem cells. And miR-200a has been known as a powerful regulator of EMT. Here, we sought to investigate the role of miR-200a in regulation of EMT phenotype of liver cancer stem cells (LCSCs). We used side population (SP) sorting to obtain cancer stem-like cells from HCC cell lines and identified that the SP fraction could be enriched with LCSCs. Then, we detected the expression of miR-200a and EMT makers in SP and non-SP cells. Our results suggested that miR-200a was down-regulated in SP cells, along with relatively low epithelial marker and high mesenchymal marker. In order to find the role of miR-200a in the manipulation of EMT, we transfected miR-200a mimic into LCSCs and found that overexpression of miR-200a resulted in down-regulation of N-cadherin, ZEB2, and vimentin, but up-regulation of E-cadherin. Moreover, overexpression of miR-200a resulted in decreased migration and invasion ability in LCSCs. In conclusion, our study revealed that miR-200a played an important role in linking the characteristics of cancer stem cells with EMT phenotype in HCC, and targeting miR-200a might be an effective strategy to weaken the invasive behavior of LCSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Cadherins / biosynthesis
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Homeodomain Proteins / biosynthesis
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Repressor Proteins / biosynthesis
  • Vimentin / biosynthesis
  • Zinc Finger E-box Binding Homeobox 2

Substances

  • Antigens, CD
  • CDH2 protein, human
  • Cadherins
  • Homeodomain Proteins
  • MIRN200 microRNA, human
  • MicroRNAs
  • Repressor Proteins
  • Vimentin
  • ZEB2 protein, human
  • Zinc Finger E-box Binding Homeobox 2