Up-regulation of miRNA-105 inhibits the progression of gastric carcinoma by directly targeting SOX9.

Abstract

MicroRNAs (miRNAs) are involved in the tumorigenesis and progression of multiple tumor types and function as either tumor suppressor genes or oncogenes. This study was designed to investigate the functional behaviors and regulatory mechanisms of miR-105 in the progression of gastric carcinoma. 24 pairs of patients with gastric carcinoma were enrolled in this study. The levels of miR-105 in gastric carcinoma tissues and cells were determined using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. The biological functions of miR-105 in gastric carcinoma cell were detected by colony formation, transwell invasion and wound-healing assay. Luciferase activity assay and immunoblotting assay were applied to validate the direct target of miR-105. The expression of SRY-Box 9 (SOX9) was detected using immunofluorescence staining assay. Furthermore, the role of miR-105 on the growth of gastric carcinoma cell was examined in the established xenograft model. The role of miR-105 in the metastasis of gastric carcinoma cell in vivo, an experimental metastasis assay was performed. Herein, we proved that miR-105 was down-regulated in gastric carcinoma specimens as well as gastric cancer cells. Up-regulation of miR-105 suppressed the colony formation and aggressiveness traits of gastric carcinoma cell lines BGC823 and SGC7901 in vitro. Furthermore, over-expression of miR-105 inhibited the tumor growth as well as lung metastasis of gastric carcinoma cell in vivo. Further investigation identified SOX9 was the target gene of miR-105 in gastric cancer and its expression was negatively associated with the expression of miR-105 in gastric carcinoma tissues. Finally, overexpression of SOX9 partially reversed the influence of miR-105 on the growth and aggressiveness of gastric carcinoma cell. These results revealed the crucial role of miR-105 in the progression and metastasis of gastric carcinoma, which indicated the potential application of miR-105 in the treatment of gastric carcinoma.