Iodine-125 irradiation inhibits invasion of gastric cancer cells by reactivating microRNA-181c expression

Iodine-125 (I-125) seed implantation has been widely used for the treatment of unresectable advanced tumors. However, the molecular mechanisms underlying the tumor-suppressive effects of I-125 irradiation have not been fully elucidated. The present study demonstrated that I-125 irradiation suppresses cell viability and inhibits cell invasiveness of gastric cancer KATO-III and MKN45 cells. Further mechanistic analysis suggested the involvement of microRNA (miR)-181c in the inhibitory effects induced by I-125 irradiation. Methylated DNA immunoprecipitation coupled with quantitative-polymerase chain reaction demonstrated that treatment with I-125 irradiation, at the dose of 4 Gy, induced promoter demethylation of the miR-181c gene in KATO-III and MKN45 cells. Following irradiation, the expression of miR-181c was significantly increased, which may be attributed to the demethylation caused by I-125 irradiation. In addition, upregulation of miR-181c by administration of miR-181c mimics decreased cell invasion, suggesting the role of miR-181c as a tumor suppressor. More importantly, the tumor-suppressive effects of I-125 irradiation were significantly compromised by the introduction of miR-181c inhibitors. Overall, these results reveal that I-125 irradiation inhibits invasiveness of gastric cancer cells by reactivating miR-181c at the epigenetic level, thereby providing important molecular evidence for the anticancer effects of I-125 irradiation.