The role and potential mechanisms of LncRNA-TATDN1 on metastasis and invasion of non-small cell lung cancer

Oncotarget. 2016 Apr 5;7(14):18219-28. doi: 10.18632/oncotarget.7788.

Abstract

The invasion and metastasis of malignant tumor cells lead to normal tissue destruction and are major prognostic factors for many malignant cancers. Long non-coding RNA (LncRNA) is associated with occurrence, development and prognoses of non-small cell lung cancer (NSCLC), but its mechanisms of action involved in tumor invasion and metastasis are not clear. In this study, we screened and detected the expression of LncRNA in two NSCLC lines 95D and 95C by using high throughput LncRNA chip. We found that TATDN1 (Homo sapiens TatD DNase domain containing 1, TATDN1), one of LncRNAs, was highly expressed in 95D cells and NSCLC tumor tissues compared to 95C cells. Knockdown of TATDN1-1 by shRNA significantly inhibited cell proliferation, adhesion, migration and invasion in 95D cells. Further mechanism study showed that TATDN1 knockdown suppressed the expression of E-cadherin, HER2, β-catenin and Ezrin. Moreover, knockdown TATDN1 also inhibited tumor growth and metastasis in a 95D mouse model in vivo by inhibiting β-catenin and Ezrin. These data indicate that TATDN1 expression is associated with 95D cells' higher potential of invasion and metastasis, and suggest that TATDN1 may be a potential prognostic factor and therapeutic target for NSCLCs.

Keywords: LncRNA; TATDN1; invasion; metastasis; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cytoskeletal Proteins / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / genetics
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • Receptor, ErbB-2 / metabolism
  • beta Catenin / metabolism

Substances

  • Cadherins
  • Cytoskeletal Proteins
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • beta Catenin
  • ezrin
  • long non-coding RNA TATDN1, human
  • ERBB2 protein, human
  • Receptor, ErbB-2