MicroRNA-126 Targeting PIK3R2 Inhibits NSCLC A549 Cell Proliferation, Migration, and Invasion by Regulation of PTEN/PI3K/AKT Pathway

Abstract

Background: Our study explored whether the microRNA-126 (miR-126)-mediated PTEN/PI3K/AKT (phosphatase and tensin homology deleted on chromosome 10/phosphatidylinositol 3-kinase regulatory subunit-β/AKT) signaling pathway by targeting PIK3R2 affects the proliferation, migration, and invasion of non-small-cell lung cancer (NSCLC) A549 cells.

Materials and methods: Quantitative real-time polymerase chain reaction was used to measure the expression of miR-126 in A549 cells. The MTT (methyl thiazolyl tetrazolium) assay, cell scratch test, Transwell assay, and Western blot were used to detect the proliferation, migration, and invasion of A549 cells and protein expression in A549 cells, respectively.

Results: The expression of miR-126 decreased and the expression of PIK3R2 increased in A549 cells (P < .05, for both). Upregulation of miR-126 resulted in the decrease of the proliferation, migration, and invasive abilities of A549 cells, the downregulation of the expression of PIK3R2, PI3K, and phosphorylated Akt (p-Akt) protein, and the upregulation of PTEN expression (P < .05 for all). Also, these abilities of A549 cells increased, and the expression of these 3 proteins was upregulated with downregulation of miR-126 (P < .05 for all). The results of the dual luciferase reporter gene assay showed that PIK3R2 was the target gene of miR-126. PIK3R2, PI3K, and p-Akt proteins were downregulated, but PTEN protein was upregulated as PIK3R2 was silenced or the inhibitor of the PTEN/PI3K/AKT signaling pathway increased. Also, downregulation of miR-126 with silencing of PIK3R2 or increasing the inhibitor of the pathway caused increased PI3K and p-Akt protein expression and increased active proliferation, migration, and invasive abilities of A549 cells (P < .05 for all).

Conclusion: The upregulation of miR-126 in NSCLC A549 cells can reduce the expression of the target gene PIK3R2 and influence the PTEN/PI3K/AKT signaling pathway, suppressing the proliferation, migration, and invasive abilities of A549 cells.

Keywords: MicroRNA-126; Non–small-cell lung cancer; Phosphatase and tensin homology deleted on chromosome 10; Phosphatidylinositol 3-hydroxy kinase; Phosphatidylinositol 3-kinase regulatory subunit-β.