STAT3 is involved in miR-124-mediated suppressive effects on esophageal cancer cells.
STAT3 is involved in miR-124-mediated suppressive effects on esophageal cancer cells.
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DOI：
10.1186/s12885-015-1303-0
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发表时间：
2015-04-19
期刊：
影响因子：
3.8
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Cheng Y;Li Y;Nian Y;Liu D;Dai F;Zhang J
食管癌（EC）是世界上最常见的癌症之一。肿瘤相关炎症通路--信号转导子和过渡期激活子3（STAT 3）信号通路在肿瘤的发生和发展中起着重要作用，但其介导的途径尚不清楚。越来越多的研究报道了microRNA（miRNAs）在基因表达调控中的重要作用，其中miR-124/STAT 3相互作用在多种肿瘤中的研究已被广泛报道，而其在EC中的作用尚未被研究。首先，我们使用双荧光素酶报告基因分析确定了STAT 3在食管癌中的靶向作用。接下来，我们探索了miR-124在EC组织中的表达。为了进一步研究其对EC细胞恶性表型的影响，我们完成了一系列实验。通过转染miR-124模拟物，可恢复食管癌细胞系Eca 109和TE-1中miR-124的表达。接下来，我们检测了miR-124异位表达对EC细胞体外增殖、细胞周期分布、凋亡、迁移和侵袭以及体内肿瘤生长的影响。双荧光素酶检测证实STAT 3是食管癌细胞中miR-124的靶基因。过表达miR-124可显著下调STAT 3的mRNA和蛋白水平。此外，我们发现miR-124的表达在食管癌组织和细胞系中始终受到抑制。接下来，功能实验表明，miR-124在EC细胞中的异位表达诱导了复杂的表型，即抑制细胞增殖、阻断G1/S期转变、诱导细胞凋亡和抑制体外细胞侵袭，以及抑制体内肿瘤生长。此外，恢复转染前miR-124的食管癌细胞中STAT 3的表达，可部分解除miR-124对Eca 109细胞增殖和侵袭的抑制作用。总的来说，这些数据表明miR-124通过至少部分靶向STAT 3信号通路在食管癌中发挥肿瘤抑制剂的作用。
Esophageal cancer (EC) is one of the most common cancers worldwide. The cancer-related inflammation pathway- signal transducer and activator of transition 3 (STAT3) signaling pathway has been reported to play critical role in its initiation and progression, while the way mediated its hyperactivation remains elusive so far. Accumulating studies reported the important role of microRNAs (miRNAs) in the regulation of gene expression, among of which, the miR-124/STAT3 interaction has been widely reported in various cancers, while its role in EC has not been investigated yet. Firstly, we identified the target role of STAT3 in esophageal cancers using Dual-luciferase reporter assays. Next, we explored the expression of miR-124 in EC tissues. To further investigate its effects on the malignant phenotype of EC cells, we completed a series of experiments. Through transfection with miR-124 mimic, the expression of miR-124 in esophageal cancer cell lines, Eca109 and TE-1, were restored. Next, we detected the effects of ectopic miR-124 expression on the proliferation, cell cycle distribution, apoptosis, migration and invasion of EC cells in vitro, and the tumor growth in vivo. Dual-luciferase assays identified that STAT3 is a target gene of miR-124 in esophageal cancer cells. Over-expression of miR-124 significantly down-regulated the mRNA and protein levels of STAT3. Moreover, we found that the expression of miR-124 was consistently suppressed in esophageal cancer tissues and cell lines. Next, functional experiments showed that ectopic expression of miR-124 in EC cells induced a complex phenotype, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, and suppression of cell invasion in vitro, as well as inhibition of tumor growth in vivo. Moreover, restored the expression of STAT3 in esophageal cancer cells transfected with miR-124 before, could partially abolished the suppressive effects of miR-124 on the proliferation and invasion of Eca109 cells. Collectively, these data suggest that miR-124 functions as a tumor suppressor in esophageal cancer through, at least partially, targeting STAT3 signaling pathway.
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