miR-502-5p affects gastric cancer progression by targeting PD-L1.

ABSTRACT

BACKGROUND: Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer. METHODS: Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot. RESULTS: The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels. CONCLUSIONS: These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.