Role of MiR-3619-5p in β-Catenin-Mediated Non-Small Cell Lung Cancer Growth and Invasion

Abstract

Background/Aims: The malignancy of non-small cell lung cancer (NSCLC) is largely due to its fast growth and invasion. WNT/β-catenin signaling plays a critical role in regulating NSCLC carcinogenesis. Hence, suppression of β-catenin signal transduction in NSCLC cells may improve the therapeutic outcome. Methods: We analyzed the levels of β-catenin and miR-3619-5p in NSCLC specimens, compared to paired non-tumor normal lung tissue (NT). We did Bioinformatics analyses on the binding sites of 3'-UTR of β-catenin mRNA by miR-3619-5p. We modified the levels of miR-3619-5p in NSCLC cells and examined their effects on β-catenin levels, and on the growth and invasion of NSCLC cells in an MTT assay and a transwell cell migration assay, respectively. Results: NSCLC specimens had significant higher levels of β-catenin, and significantly lower levels of miR-3619-5p, compared to NT. The levels of β-catenin and miR-3619-5p were inversely correlated in NSCLC specimens. Bioinformatics analyses showed that miR-3619-5p bound to 3'-UTR of β-catenin mRNA in NSCLC cells to inhibit its translation. Overexpression of miR-3619-5p decreased β-catenin protein, while depletion of miR-3619-5p increased β-catenin protein in NSCLC cells, without altering β-catenin mRNA levels. Overexpression of miR-3619-5p in NSCLC cells inhibited cell growth and invasion, while depletion of miR-3619-5p in NSCLC lines increased cell growth and invasion. Conclusion: Our data demonstrate a previously unappreciated role for miR-3619-5p in suppression of β-catenin-mediated cancer growth and invasion in NSCLC cells, and highlight miR-3619-5p as a novel cancer suppressor in NSCLC.

Keywords

• Non-small cell lung cancer (NSCLC)
• β-catenin
• MiR-3619-5p
• Bioinformatics analyses
• miRNAs