LncRNA MALAT1 promotes epithelial-to-mesenchymal transition of esophageal cancer through Ezh2-Notch1 signaling pathway

Anticancer Drugs. 2018 Sep;29(8):767-773. doi: 10.1097/CAD.0000000000000645.

Abstract

To investigate effect of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on epithelial-to-mesenchymal transition (EMT) of esophageal cancer (EC) and role of enhancer of zeste homolog 2 (Ezh2)-Notch1 signaling pathway in the process. The expression of MALAT1 was determined in four EC cell lines by real-time PCR. TE-1 and EC109 cells were transfected with sh-MALAT1 to inhibit expression of MALAT1 or transfected with pcDNA3.1-Ezh2 to overexpress Ezh2. Invasion and migration assays were conducted to analyze cell metastasis, and expressions of Ezh2-Notch1 signaling-related proteins as well as EMT related proteins were determined using both real-time PCR and western blot. MALAT1 was significantly up-regulated in all EC cell lines compared with the normal cells. Silencing MALAT1 using shRNA could significantly inhibit cell viability (reduced almost 30% of cell viability compared with the control), invasion (reduced almost 30% of cell migration compared with the control), and migration (reduced almost 50% of cell migration compared with the control) of both TE-1 and EC109 cells (P<0.05). Meanwhile, expression of Ezh2, Notch1, Hes1, MMP-9, and Vimentin was significantly decreased and expression of E-cadherin was significantly increased when cells were transfected with sh-MALAT1 compared with the nontransfected cells (P<0.05). However, when cells were cotransfected with both sh-MALAT1 and pcDNA3.1-Ezh2, the protein expression changes induced by sh-MALAT1 were recovered. MALAT1 could affect EMT and metastasis of EC cells through Ezh2-Notch1 signaling pathway. This study can give deeper understandings of the role of MALAT1 in EC and may provide some new directions for treatment of patients with EC.

MeSH terms

  • Cell Line, Tumor
  • Enhancer of Zeste Homolog 2 Protein / biosynthesis
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism*
  • Epithelial-Mesenchymal Transition / genetics
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Gene Silencing
  • Humans
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase 9 / genetics
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Receptor, Notch1 / biosynthesis
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Signal Transduction
  • Transcription Factor HES-1 / biosynthesis
  • Transcription Factor HES-1 / genetics
  • Transfection
  • Vimentin / biosynthesis
  • Vimentin / genetics

Substances

  • MALAT1 long non-coding RNA, human
  • NOTCH1 protein, human
  • RNA, Long Noncoding
  • Receptor, Notch1
  • Transcription Factor HES-1
  • VIM protein, human
  • Vimentin
  • HES1 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • MMP9 protein, human
  • Matrix Metalloproteinase 9