UTMD-mediated delivery of miR-21-5p inhibitor suppresses the development of lung cancer

Abstract

Background: Ultrasound-targeted microbubble destruction (UTMD) is a new type of gene delivery technology. MiR-21-5p was highly expressed in a variety of cancers. In this paper, miR-21-5p inhibitor was transfected into lung cancer cells by UTMD to observe its role in lung cancer.Methods: StarBase was used to analyze the miR-21-5p expression in lung cancer patients and its relationship with the prognosis of the patients. MiR-21-5p expression in lung cancer tissues or cell lines was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Effects of gradient concentration (0, 5, 10, 20, 30%) of SonoVue or gradient mechanical index (MI) (0, 0.5, 1, 1.5, 2 W/cm2) on the cell viability were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The targeting relationship between miR-21-5p and B-cell translocation gene 2 (BTG2) was predicted by TargetScan and confirmed by dual-luciferase reporter assay, while the expressions of the two genes were determined by qRT-PCR. Through liposome transfection or UTMD transfection, the effects of miR-21-5p/BTG2 on the biological behaviors of lung cancer cells, the size of xenograft tumors and the expressions of ki67 and miR-21-5p were measured by qRT-PCR, western blot, cell function experiments and immunohistochemistry, respectively.Results: MiR-21-5p expression was upregulated in lung cancer, which was associated with a poor prognosis. The optimal ultrasound conditions were 10% SonoVue concentration and 1 W/cm2. UTMD transfection exerted a stronger effect than liposome transfection. MiR-21-5p promoted cell viability, proliferation and migration yet suppressed apoptosis by targeting BTG2. MiR-21-5p inhibitor reduced the size and volume of xenograft tumor and the expressions of ki67 and miR-21-5p in xenograft tumor tissues. ConclusionUTMD-mediated miR-21-5p inhibitor can more effectively suppress the development of lung cancer.