title: Loss of RACK1 Promotes Metastasis of Gastric Cancer by Inducing a miR-302c/IL8 Signaling Loop.
abstract: Gastric cancer remains the third leading cause of cancer-related mortality worldwide, and invasion and metastasis of gastric cancer represent the major reason for its poor prognosis. In this study, we found that loss of the receptor for activated C-kinase 1 (RACK1) promoted the metastasis of gastric cancer by enhancing the autocrine expression of IL8 in vitro and in vivo. microRNA (miRNA; miR) array identified that RACK1 modulated the expression of a series of miRNAs, including the miR-302 cluster, and RACK1 modulated the IL8 expression and tumor invasion through miRNA-302c. Moreover, upregulation of IL8 in turn decreased the level of miRNA-302c and induced IL8 expression in a feedback manner. Tissue microarray also indicated that RACK1 was correlated with invasion/metastasis phenotype, IL8 expression, as well as 5-year survival in clinical cases of gastric cancer. Together, our results imply that loss of RACK1 in gastric cancer links epigenetics to inflammatory cytokines to promote tumor metastasis.
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Lingqiang
authors.initials: L
authors.lastname: Min
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Statistics, Oklahoma State University, Stillwater, Oklahoma.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Qiangjun
authors.initials: Q
authors.lastname: Gan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China. sun.yihong@zs-hospital.sh.cn qin.xinyu@zs-hospital.sh.cn yuanyuanruan@fudan.edu.cn.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. sun.yihong@zs-hospital.sh.cn qin.xinyu@zs-hospital.sh.cn yuanyuanruan@fudan.edu.cn.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. sun.yihong@zs-hospital.sh.cn qin.xinyu@zs-hospital.sh.cn yuanyuanruan@fudan.edu.cn.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019898:Autocrine Communication; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics*; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010534:Peritoneal Neoplasms / Q000556:secondary; D034741:RNA, Small Interfering / Q000494:pharmacology; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053700:Receptors, Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*
chemical_list: D016209:Interleukin-8; C558265:MIRN302 microRNA, mouse; D035683:MicroRNAs; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D034741:RNA, Small Interfering; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D053700:Receptors, Interleukin-8; D019204:GTP-Binding Proteins