Effect of TET1 gene expression on migration and invasion in lung cancer cells

Abstract

Objective To explore the effect of ten-eleven translocation family 1 (TET1) gene expression on the migration and invasion of lung cancer cells and investigate its underlying mechanism. Methods The expression level of TET1 gene in normal human bronchial epithelial (HBE) cells and lung cancer cell lines (H460, H358, 95D and LTEP-a-2) was detected by quantitative RT-PCR. The effects of different expression level (overexpression and knockdown) of TET1 gene on the migration and invasion ability in lung cancer cells was analyzed by wound healing experiment and Transwell assay. The mRNA and protein expression levels of downstream regulatory gene β-catenin (CTNNB1) and MMP7 were detected by quantitative RT-PCR and Western blotting to determine the possible signal pathway. Results The expression level of TET1 gene was decreased in lung cancer cells compared with normal HBE cells (P < 0.01). Overexpression of TET1 gene significantly inhibited the migration and invasion of lung cancer cells, while its knockdown enhanced the invasion and migration abilities of lung cancer cells (P < 0.01). The mRNA and protein expression levels of CTNNB1 and MMP7 were decreased after TET1 overexpression, while the mRNA and protein levels of the 2 molecules were increased after knockdown (P < 0.01). Blockade of CTNNB1 by its inhibitor significantly diminished the effect of TET1 on the migration and invasion of lung cancer cell lines. Conclusion The expression level of TET1 is down-regulated in lung cancer cell lines. TET1 gene may inhibit the migration and invasion of lung cancer cells mainly through Wnt/β-catenin signaling pathway and its key downstream genes CTNNB1 and MMP7.

Keywords

• tet1 gene
• lung cancer
• migration
• invasion
• wnt/β-catenin signaling pathway