Gastric Cancer Cell Proliferation and Survival Is Enabled by a Cyclophilin B/STAT3/miR-520d-5p Signaling Feedback Loop
Gastric Cancer Cell Proliferation and Survival Is Enabled by a Cyclophilin B/STAT3/miR-520d-5p Signaling Feedback Loop
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亲环蛋白 B/STAT3/miR-520d-5p 信号反馈环促进胃癌细胞增殖和存活
DOI：
10.1158/0008-5472.can-16-0357
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发表时间：
2017-03-01
期刊：
影响因子：
11.2
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Li, Ting;Guo, Hanqing;Fan, Daiming
尽管其致病性很强，但仍不为人知。由IL 6和其他促炎细胞因子激活的JAK 2/STAT 3通路作为癌症发病机制中的关键环节而受到关注，但其在癌细胞中激活的基础尚不清楚。在此我们报道了IL 6触发的反馈环调节胃癌细胞的生长和存活，该反馈环涉及STAT 3介导的miR-520 d-5 p的抑制及其下游靶点亲环素B（CypB）的上调。在胃癌的临床标本中，我们记录了CypB的表达增加和STAT 3的激活。机制研究将miR-520 d-5 p鉴定为CypB mRNA水平的调节剂。该信号传导轴通过调节STAT 3的磷酸化来调节胃癌的生长。此外，miR-520 d-5 p被鉴定为直接STAT 3靶标，并且IL 6介导的miR-520 d-5 p抑制依赖于STAT 3活性。我们的研究结果定义了一个正反馈回路，驱动胃癌的影响H。幽门螺杆菌感染涉及促炎性IL 6刺激。(C)2016年AACR。
obscure despite their great pathogenic significance. The JAK2/STAT3 pathway activated by IL6 and other proinflammatory cytokines has garnered attention as a pivotal link in cancer pathogenesis, but the basis for its activation in cancer cells is not understood. Here we report that an IL6-triggered feedback loop involving STAT3-mediated suppression of miR-520d-5p and upregulation of its downstream target cyclophilin B ( CypB) regulate the growth and survival of gastric cancer cells. In clinical specimens of gastric cancer, we documented increased expression of CypB and activation of STAT3. Mechanistic investigations identified miR-520d-5p as a regulator of CypB mRNA levels. This signaling axis regulated gastric cancer growth by modulating phosphorylation of STAT3. Furthermore, miR-520d-5p was identified as a direct STAT3 target and IL6-mediated inhibition of miR-520d-5p relied upon STAT3 activity. Our findings define a positive feedback loop that drives gastric carcinogenesis as influenced by H. pylori infections that involve proinflammatory IL6 stimulation. (C) 2016 AACR.