c-Met and CREB1 are involved in miR-433-mediated inhibition of the epithelial-mesenchymal transition in bladder cancer by regulating Akt/GSK-3β/Snail signaling.
c-Met and CREB1 are involved in miR-433-mediated inhibition of the epithelial-mesenchymal transition in bladder cancer by regulating Akt/GSK-3β/Snail signaling.
复制标题
c-Met 和 CREB1 通过调节 Akt/GSK-3beta/Snail 信号传导参与 miR-433 介导的膀胱癌上皮间质转化抑制。
DOI：
10.1038/cddis.2015.274
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发表时间：
2016-02-04
影响因子：
9
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Xu X;Zhu Y;Liang Z;Li S;Xu X;Wang X;Wu J;Hu Z;Meng S;Liu B;Qin J;Xie L;Zheng X
越来越多的证据表明microRNAs（miRNAs）通过调节多种细胞通路在肿瘤的发生和发展中发挥重要作用。本文就miR-433在膀胱癌（BCa）中的作用及其调控网络进行综述。与邻近的非癌组织相比，miR-433在BCa组织中经常下调。表观遗传学机制可能参与了miR-433表达的调控。miR-433的增强表达显著抑制BCa细胞的增殖、集落形成、迁移和侵袭。此外，miR-433通过调节c-Met/Akt/GSK-3β/Snail信号通路抑制BCa细胞的上皮-间质转化（EMT）。c-Met和CREB 1都是miR-433的下游靶基因。CREB 1还可通过MITF间接调节c-Met/Akt/GSK-3β/Snail信号通路。此外，CREB 1表达是BCa患者总生存期的独立预后因素。最后，c-Met和miR-433/miR-409- 3 p之间似乎存在相互调节。综上所述，这项研究揭示了miR-433-c-MET/CREB 1-Akt/GSK-3β/Snail信号传导对BCa中的EMT至关重要。靶向本文所述的途径可能为限制BCa的转移进展开辟新的前景。
Emerging evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse cellular pathways. Here we describe the function and regulation network of miR-433 in bladder cancer (BCa). miR-433 is frequently downregulated in BCa tissues compared with adjacent non-cancerous tissues. Epigenetic mechanisms may be involved in the regulation of miR-433 expression. Enforced expression of miR-433 significantly inhibits proliferation, colony formation, migration, and invasion in BCa cells. In addition, miR-433 inhibits the epithelial–mesenchymal transition (EMT) in BCa cells by regulating c-Met/Akt/GSK-3β/Snail signaling pathway. Both c-Met and CREB1 are downstream target genes of miR-433. CREB1 can also indirectly regulate c-Met/Akt/GSK-3β/Snail signaling via MITF. Furthermore, CREB1 expression is an independent prognostic factor for overall survival in patients with BCa. Finally, there appears to exist a reciprocal regulation between c-Met and miR-433/miR-409-3p. Taken together, this study reveals that miR-433-c-MET/CREB1-Akt/GSK-3β/Snail signaling is critical to EMT in BCa. Targeting the pathway described here may open up new prospects to restrict metastatic progression of BCa.