LncRNA TTN-AS1 drives invasion and migration of lung adenocarcinoma cells via modulation of miR-4677-3p/ZEB1 axis

J Cell Biochem. 2019 Oct;120(10):17131-17141. doi: 10.1002/jcb.28973. Epub 2019 Jun 7.

Abstract

Lung adenocarcinoma is the most prevalent type of lung cancer with a high incidence and mortality worldwide. Metastasis is the major cause of high death rate in lung cancer and the potential mechanism of lung adenocarcinoma metastasis remains indistinct. Emerging investigations have demonstrated that long noncoding RNA is a kind of non-protein coding RNA and plays a critical role in cancer progression and metastasis. TTN antisense RNA 1 (TTN-AS1) has been reported to promote cell growth and metastasis in cancer. However, the function of TTN-AS1 in lung adenocarcinoma is still to be illustrated. In this study, we observed that TTN-AS1 was upregulated in tissues and cells of lung adenocarcinoma and associated with poor overall survival. TTN-AS1 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition in lung cancer. TTN-AS1 directly bound with miR-4677-3p and negatively regulated miR-4677-3p. MiR-4677-3p rescued the inhibitive impacts of TTN-AS1 knockdown on lung adenocarcinoma. Furthermore, zinc finger E-box binding homeobox 1 (ZEB1) was the target of miR-4677-3p, and TTN-AS1 modulated ZEB1 by competing for miR-4677-3p. TTN-AS1 drove the invasion and migration of lung adenocarcinoma cells by targeting the miR-4677-3p/ZEB1 axis. To sum up, our study offers insights into the mechanism of TTN-AS1 in lung adenocarcinoma metastasis and targeting the TTN-AS1/miR-4677-3p/ZEB1 axis may be the potential innovate therapeutic strategy for the patients with lung adenocarcinoma.

Keywords: TTN-AS1; ZEB1; lncRNA; lung adenocarcinoma; metastasis; miR-4677-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / metabolism
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Base Pairing
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Connectin / genetics*
  • Connectin / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction
  • Survival Analysis
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • Connectin
  • MIRN46773p microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TTN protein, human
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1