hTERT mediates gastric cancer metastasis partially through the indirect targeting of ITGB1 by microRNA-29a

Sci Rep. 2016 Feb 23:6:21955. doi: 10.1038/srep21955.

Abstract

Human telomerase reverse transcriptase (hTERT) plays a key role in tumor invasion and metastasis, but the mechanism of its involvement in these processes is not clear. The purpose of this study is to investigate the possible molecular mechanism of hTERT in the promotion of gastric cancer (GC) metastasis. We found that the up-regulation of hTERT in gastric cancer cells could inhibit the expression of miR-29a and enhance the expression of Integrin β1 (ITGB1). In addition, the invasive capacity of gastric cancer cells was also highly increased after hTERT overexpression. Our study also found that the restoration of miR-29a suppressed the expression of ITGB1 and inhibited GC cell metastasis both in vitro and in vivo. Taken together, our results suggested that hTERT may promote GC metastasis through the hTERT-miR-29a-ITGB1 regulatory pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aged
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Injections, Subcutaneous
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery
  • Survival Analysis
  • Telomerase / genetics*
  • Telomerase / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • ITGB1BP1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN29a microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • TERT protein, human
  • Telomerase