RAB31 Targeted by MiR-30c-2-3p Regulates the GLI1 Signaling Pathway, Affecting Gastric Cancer Cell Proliferation and Apoptosis

Background:Gastric cancer (GC), one of the most common cancers worldwide, is highly malignant and fatal. RAB31, a member of the RAB family of oncogenes, participates in the process of carcinogenesis and cancer development. However, the underlying role of RAB31 in GC progression remains unknown. Methods：In our study, 90 pairs of tissue microarrays were used to measure the level of RAB31 protein by immunochemistry assay and 22 pairs of fresh tissue were used to measure the level of RAB31 mRNA. We investigated the effect of RAB31 on tumor growth in vitro and in vivo. Results: RAB31 was overexpressed in GC tissues, and the overexpression of RAB31 predicted poor survival. In a nude mouse model, we found that depletion of RAB31 inhibited tumor growth. In vitro, silencing of RAB31 suppressed cell viability, promoted cell cycle arrest, and enhanced cell apoptosis. Further, cell cycle and apoptotic protein expression was subsequently reduced; these effects were mediated by GLI1. More importantly, co-IP and Immunofluorescence assays confirmed that RAB31 interacted with GLI1. In addition, via luciferase reporter assay and Western blotting, we found that miR-30c-2-3p modulates the RAB31/GLI1 pathway through the targeting of the 3’-UTR of RAB31. Conclusions: Collectively, these data show that RAB31 was regulated by miR-30c-2-3p and functioned as an oncogene in GC tumorigenesis and development via interacting with GLI1. Therefore, the targeting of miR-30c-2-3p/RAB31/GLI1 axis may be regarded as a therapeutic intervention in gastric cancer.