Nanoparticles-encapsulated miR-126 inhibits invasion and metastasis of lung cancer through epidermal growth factor receptor/protein kinase B/mammalian target of rapamycin signaling via targeting of SOX4

Abstract

miR-126 is involved in lung cancer progression. This study explored effects of miR-126 with arsenic trioxide nanoparticles as a carrier on lung cancer cell invasion and metastasis, and possible molecular mechanisms. Four groups, including blank group, positive control group, miR-126 group, and epidermal growth factor receptor (EGFR)/protein kinase B (AKT)/Mammalian target of rapamycin (mTOR) (EGFR/AKT/mTOR) signal pathway activation group (agonist group) were set. Positive control group was treated with anticancer drug paclitaxel. Cells in miR-126 group were transfected with nanoparticle-encapsulated miR-126, while cells in the agonist group were treated with EGFR/AKT/mTOR signal pathway agonist. Cell metastasis, invasion, EGFR/AKT/mTOR signaling pathway activity, expressions of N-cadherin, Vimentin, MMP-9, MMP-2, SOX4, EGFR, and AKT and mTOR were measured, and relationship between miR-126 and SOX4 was investigated. Agonist treatment significantly increased metastasis, while miR-126 transfection significantly decreased cell invasion and metastasis (P < 0.05). Compared to blank and agonist group, the expressions of N-cadherin, Vimentin, MMP-9, MMP-2, SOX4, EGFR, AKT, and mTOR were down-regulated in miR-126 group and PC group (P < 0.05). In contrast, E-cadherin was up-regulated (P < 0.05). miR-126 was bound to 3′UTR of SOX4. Moreover, the miR-126 decreased SOX4 protein, thereby inhibiting the EGFR signaling pathway, suppressing EGFR to further inhibit AKT and mTOR expression, and finally inhibiting lung cancer progression. Its molecular mechanism is mainly related to suppression of EGFR/AKT/mTOR signaling.