Loss of RACK1 Promotes Metastasis of Gastric Cancer by Inducing a miR-302c/IL8 Signaling Loop
Loss of RACK1 Promotes Metastasis of Gastric Cancer by Inducing a miR-302c/IL8 Signaling Loop
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RACK1 缺失通过诱导 miR-302c/IL8 信号环路促进胃癌转移。
DOI：
10.1158/0008-5472.can-14-3690
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发表时间：
2015-09-15
期刊：
影响因子：
11.2
通讯作者：
Gu, Jianxin
中科院分区：
文献类型：
--
作者：
Chen, Ling;Min, Lingqiang;Gu, Jianxin
胃癌仍然是全球第三大癌症相关死亡原因，而胃癌的侵袭和转移是其预后不良的主要原因。在本研究中，我们发现活化C-激酶1受体(RACK1)的缺失可能通过促进IL-8在体内外的自分泌而促进胃癌的转移。MicroRNA(miRNA；miR)芯片发现RACK1调控包括miR-302簇在内的一系列miRNAs的表达，RACK1通过miRNA-302C调控IL8的表达和肿瘤的侵袭。此外，IL8的上调反过来降低了miRNA-302C的水平，并以反馈的方式诱导IL8的表达。组织芯片显示RACK1与胃癌的侵袭/转移表型、IL-8表达及5年生存率相关。综上所述，我们的结果表明，RACK1在胃癌中的缺失将表观遗传学与炎性细胞因子联系起来，以促进肿瘤转移。(C)2015年AACR。
Gastric cancer remains the third leading cause of cance-rrelated 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 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. (C) 2015 AACR.