Tumor Suppressor MiR-22 Suppresses Lung Cancer Cell Progression Through Post-transcriptional Regulation of ErbB3

Background: Development of efficient therapies of lung cancer and deep understanding of their anti-tumor mechanism are very important. The aim of the present study is to investigate the therapeutic effect of microRNA-22 (miR-22) on lung cancer using in vitro and in vivo methods.

Methods: Expression level of miR-22 in lung cancer specimens and relative normal tissues was detected by microRNA-specific quantitative real-time PCR (Q-PCR). Invasion assay, cell counting kit-8 assay, and Annexin V/7-AAD analysis were performed to test the invasion and proliferation of lung cancer cell after transfection. The effect of miR-22 on lung cancer in vivo was validated by murine xenograft model.

Results: Q-PCR detection of miR-22 in clinical samples showed that the relative expression level of miR-22 in lung cancer tissues and lung cancer cell lines was lower than that in normal tissues. Transfection of miR-22 expression plasmids could significantly inhibit the increased cell numbers and invasion of A549 and H1299 lung cancer cell lines. Furthermore, miR-22 was demonstrated to inhibit the expression of ErbB3 through post-transcriptional regulation via binding to ErbB3 3'-UTR. Co-transfection of ErbB3 expression plasmid could promote the proliferation and invasion of A549 and H1299. In vivo experiments using nude mice demonstrated that over-expression of miR-22 could significantly decrease the volume and weight of tumors.

Conclusions: miR-22 exhibited excellent anti-lung cancer activity in vitro and in vivo, and post-transcriptional regulation of ErbB3 might be a potential mechanism.