Odd-skipped related 1 inhibits lung cancer proliferation and invasion by reducing Wnt signaling through the suppression of SOX9 and β-catenin

Abstract

The odd-skipped related 1 (OSR1) gene encodes a zinc-finger transcription factor. The expression and significance of OSR1 in human tumors remains unclear. We found that OSR1 was downregulated in lung cancers, and its expression was correlated with poor differentiation. Overexpression of OSR1 by OSR1 gene transfection into H1299 cells (H1299-OSR1) inhibited the proliferation and invasion of lung cancer cells. Knockdown of OSR1 with small interfering (si)RNA against OSR1 in A549 cells (A549-siOSR1) enhanced the proliferation and invasion of lung cancer cells. Western blot analysis showed that the expression level of GSK3β increased, while that of p-GSK3β, nuclear β-catenin, cyclin D1, c-Myc and matrix metallopeptidase 7 significantly decreased in the H1299-OSR1 cells, and this pattern was reversed in the A549-siOSR1 cells compared to that in the control cells. Furthermore, upregulation of sex-determining region Y-box 9 (SOX9) by SOX9 gene transfection increased the expression of β-catenin, which was inhibited by OSR1. The mRNA and protein expression levels of SOX9 and β-catenin were reduced in H1299-OSR1 cells and increased in A549-siOSR1 cells. In conclusion, the expression of OSR1 was more reduced in lung cancer tissues than in normal lung tissues, and was correlated with poor differentiation. OSR1 downregulated the activity of the Wnt signaling pathway by suppressing the expression of SOX9 and β-catenin.