Ral GTPases targeted by miR-215-5p promote lung cancer proliferation and migration
Abstract Background The Ras-like guanosine triphosphatases (Ral GTPases) belongs to the Ras superfamily of small GTPases. Ras mutations occur in more than one in three human tumors. However, treatments acting directly on Ras post-translational modifications were developed and have been manufactured for many years, although they have demonstrated poor clinical performance. Ral GTPases include RalA and RalB, seem to be a new potential pathway downstream of mutant Ras. Methods In this study, we examined protein and mRNA level of Ral GTPases in lung specimens from 12 lung cancer patients using Western Blot and RT-PCR. The effects of RalA and RalB on the proliferation and migration were examined by functional tests in vitro and in vivo. The binding site in miR-215-5p and RalA or RalB was predicted using bioinformatics software and proved by Western Blot, RT-PCR and luciferase assay. The effect of miR-215-5p on RalA and RalB were examined in cell lines and xenograft mice. Results Here, we reported that miR-215-5p was downregulated in human lung cancer tissues compared with noncancerous tissues, whereas the expression level of Ral GTPases was higher. We further verified that the negative regulation of Ral GTPases by miR-215-5p could inhibit the proliferation and migration of lung cancer in vitro and in vivo. Conclusion In this study, we reported that RalA and RalB promote lung cancer proliferation and migration. Moreover, we identified miR-215-5p as a tumor suppressor that targets Ral GTPases. Our results may offer therapeutic opportunities in lung cancer.