MiR-505 Acts As a Tumor Suppressor in Gastric Cancer Progression Through Targeting HMGB1

Gastric cancer (GC) is a frequent type of malignant tumor worldwide. GC metastasis results in the majority of clinical treatment failures. MicroRNAs (miRNA) are identified to exhibit crucial roles in GC. Our current study aimed to explore the biological roles of miR-505 in GC progression. It was observed that miR-505 was robustly decreased in GC cells compared with human normal gastric epithelial GES-1 cells. Overexpression of miR-505 was able to repress GC progression in AGS and BGC-823 cells. In addition, high-mobility group box 1 (HMGB1) has been identified as a crucial oncogene in several cancer types. By carrying out bioinformatics analysis, HMGB1 was predicted as a direct target of miR-505. Meanwhile, HMGB1 was found to be significantly increased in GC cells and it was confirmed in our study that miR-505 can directly target HMGB1 in vitro. miR-505 mimics can inhibit HMGB1 messenger RNA and protein expression dramatically. Subsequently, knockdown of HMGB1 can inhibit GC cell proliferation, colony formation, and induce cell apoptosis. Furthermore, HMGB1 silence suppressed GC cell migration and invasion greatly in vitro. Finally, it was validated that miR-505 can inhibit GC progression by targeting HMGB1 in vivo. Taken these together, it was indicated that miR-505/HMGB1 axis was involved in the development of GC. miR-505 can serve as a potential prognostic indicator in GC therapy.