miR-9500 Regulates Migration and Invasion of Lung Adenocarcinoma Cells by Targeting SMAD2

Objective  To explore the molecular mechanism underlying miR-9500 regulating the migration and invasion of lung adenocarcinoma cells by targeting SMAD2.

Methods  The core target genes of miR-9500 were screened out by bioinformatics analysis, and their GO function analysis, KEGG signaling pathway enrichment, and survival analysis were performed. The targeted binding sites between miR-9500 and SMAD2 were predicted, and the direct targeting relationship between miR-9500 and SMAD2 was verified by dual-luciferase reporter assay. qRT-PCR and Western blot were used to assess the effect of miR-9500 on the mRNA and protein expression levels of SMAD2. Wound healing assay, Transwell assay, and Matrigel invasion assay were used to determine the effect of miR-9500 on the migration and invasion of lung adenocarcinoma cells.

Results  The core target genes of miR-9500 were mainly enriched in the cancer pathway, TGF-β signaling pathway, and focal adhesion. However, only the expression levels of VAMP2, SMAD2, and RXRA among the top 10 core target genes were significantly correlated with the overall survival of patients with lung adenocarcinoma. miR-9500 targeted SMAD2 and down-regulated the expression levels of SMAD2, and overexpression of miR-9500 significantly inhibited the migration and invasion of lung adenocarcinoma cells and markedly decreased the expression levels of MMP2 and MMP9.

Conclusion  miR-9500 can inhibit the migration and invasion of lung adenocarcinoma cells by targeting SMAD2, which may play an important role in the tumorigenesis and development of lung adenocarcinoma as a tumor suppressor.