title: Iodine-125 irradiation inhibits invasion of gastric cancer cells by reactivating microRNA-181c expression.
abstract: Iodine-125 (125I) seed implantation has been widely used for the treatment of unresectable advanced tumors. However, the molecular mechanisms underlying the tumor-suppressive effects of125I irradiation have not been fully elucidated. The present study demonstrated that125I 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 by125I irradiation. Methylated DNA immunoprecipitation coupled with quantitative-polymerase chain reaction demonstrated that treatment with125I 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 by125I 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 of125I irradiation were significantly compromised by the introduction of miR-181c inhibitors. Overall, these results reveal that125I irradiation inhibits invasiveness of gastric cancer cells by reactivating miR-181c at the epigenetic level, thereby providing important molecular evidence for the anticancer effects of125I irradiation.
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Department of Vascular Surgery, Fourth Affiliated Hospital to Kunming Medical University, Kunming, Yunnan 650021, P.R. China; Vascular Surgery Centre in Yunnan, Kunming, Yunnan 650021, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Department of Vascular Surgery, Fourth Affiliated Hospital to Kunming Medical University, Kunming, Yunnan 650021, P.R. China; Vascular Surgery Centre in Yunnan, Kunming, Yunnan 650021, P.R. China.
authors.forename: Zhen-Huan
authors.initials: ZH
authors.lastname: Ma
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Abdominal Surgery Centre, The Health and Family Planning Commission of Yunnan Kunming, Kunming, Yunnan 650021, P.R. China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Abdominal Surgery Centre, The Health and Family Planning Commission of Yunnan Kunming, Kunming, Yunnan 650021, P.R. China.
authors.forename: Wan-Fu
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Department of Vascular Surgery, Fourth Affiliated Hospital to Kunming Medical University, Kunming, Yunnan 650021, P.R. China; Vascular Surgery Centre in Yunnan, Kunming, Yunnan 650021, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Department of Vascular Surgery, Fourth Affiliated Hospital to Kunming Medical University, Kunming, Yunnan 650021, P.R. China; Vascular Surgery Centre in Yunnan, Kunming, Yunnan 650021, P.R. China.
authors.forename: Ling-Juan
authors.initials: LJ
authors.lastname: Du
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Department of Vascular Surgery, Fourth Affiliated Hospital to Kunming Medical University, Kunming, Yunnan 650021, P.R. China; Vascular Surgery Centre in Yunnan, Kunming, Yunnan 650021, P.R. China.
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Department of Vascular Surgery, Fourth Affiliated Hospital to Kunming Medical University, Kunming, Yunnan 650021, P.R. China; Vascular Surgery Centre in Yunnan, Kunming, Yunnan 650021, P.R. China.
authors.forename: Guo-Kai
authors.initials: GK
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan, Kunming, Yunnan 650021, P.R. China; Department of Vascular Surgery, Fourth Affiliated Hospital to Kunming Medical University, Kunming, Yunnan 650021, P.R. China; Vascular Surgery Centre in Yunnan, Kunming, Yunnan 650021, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
keywords: 125I irradiation; DNA methylation; gastric cancer; invasion; miRNA; microRNA