MET/SMAD3/SNAIL circuit mediated by miR-323a-3p is involved in regulating epithelial-mesenchymal transition progression in bladder cancer.
MET/SMAD3/SNAIL circuit mediated by miR-323a-3p is involved in regulating epithelial-mesenchymal transition progression in bladder cancer.
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miR-323a-3p介导的MET/SMAD3/SNAIL回路参与调节膀胱癌上皮间质转化进展
DOI：
10.1038/cddis.2017.331
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发表时间：
2017-08-24
影响因子：
9
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Li J;Xu X;Meng S;Liang Z;Wang X;Xu M;Wang S;Li S;Zhu Y;Xie B;Lin Y;Zheng X;Liu B;Xie L
膀胱癌(BCA)是最常见的癌症之一，发病率高、发生率高、5年生存率低。新的证据表明，DLK1-dio3基因组区域尤其是该区域的miRNA簇参与了多种病理过程和多种癌症的发生，miR-323A-3p就是该miRNA簇的成员。本研究探讨miR-323A-3p在BCA中的功能及其调控网络。与邻近非肿瘤组织和膀胱正常细胞系(SV-Huc-1)相比，MIR-323A-3p在BCA组织和三种细胞系中表达下调。此外，miR-323A-3p的下调与BCA的总体生存率显著相关。DLK1-MEG3基因间DMR(IG-DMR)的甲基化有助于miR-323A-3p的还原。MiR-323A-3p的过表达显著抑制了BCA的上皮-间充质转化(EMT)进程。上调的MET和Smad3都是miR-323A-3p的直接靶点，MET和Smad3的下调也抑制了EMT的进展，并与miR-323A-3p的过表达一致。在MET和SMAD3信号的最后一个靶向共聚焦蛋白中检测到蜗牛，从而触发EMT。因此，建立了miR-323A-3p/MET/Smad3/Snail电路来调节BCA的EMT进程。MiR-323A-3P/miR-433/miR-409与MET之间的相互调控机制也参与了这一循环。总之，我们的研究证实了miR-323A-3p/Met/Smad3/Snail通路参与BCA的EMT调控的一种新的调控机制，这可能是BCA潜在的治疗靶点。
Bladder cancer (BCa) is the one of the most common cancers with high incidence, occurrence and low 5-year survival rate. Emerging evidence indicates that DLK1-DIO3 genomic region especially the miRNA cluster in this region is involved in several pathologic processes and various cancers, and miR-323a-3p is a member of this miRNA cluster. In this study, we investigate the function and regulatory network of miR-323a-3p in BCa. miR-323a-3p is frequently downregulated in BCa tissues and three cell lines compared with adjacent non-tumorous tissues and bladder normal cell line (SV-HUC-1). Besides, downregulation of miR-323a-3p is significantly associated with poor overall survival rate of BCa. Methylation of DLK1-MEG3 intergenic DMR (IG-DMR) contributes to the reduction of miR-323a-3p. Overexpression of miR-323a-3p significantly inhibits the epithelial–mesenchymal transition (EMT) progression of BCa. Both upregulated MET and SMAD3 are direct targets of miR-323a-3p, and the knockdown of MET and SMAD3 also represses the EMT progression consistently with overexpression of miR-323a-3p. SNAIL is detected in the last targeted confocal protein of both MET and SMAD3 signaling that trigger EMT consequently. Hence, a miR-323a-3p/MET/SMAD3/SNAIL circuit is established to regulate the EMT progression of BCa. And a mutual regulatory mechanism between miR-323a-3p/miR-433/miR-409 and MET also participates in this circuit. In conclusion, our study demonstrates a novel regulatory mechanism of the miR-323a-3p/MET/SMAD3/SNAIL circuit that is involved in the EMT regulation of BCa, which may be a potential therapy target for BCa.
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影响因子：
3.8
作者：
Lehner B;Kunz P;Saehr H;Fellenberg J
通讯作者：
Fellenberg J
RASAL2 是一种 RAS GTP 酶激活蛋白，通过 MAPK/SOX2 通路抑制膀胱癌的干细胞性和上皮间质转化。
影响因子：
9
作者：
Hui K;Gao Y;Huang J;Xu S;Wang B;Zeng J;Fan J;Wang X;Yue Y;Wu S;Hsieh JT;He D;Wu K
通讯作者：
Wu K
影响因子：
--
作者：
Hitachi K;Tsuchida K
通讯作者：
Tsuchida K
DOI：
10.1186/s12964-017-0165-2
发表时间：
2017-02-17
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Hass R;Jennek S;Yang Y;Friedrich K
通讯作者：
Friedrich K
影响因子：
3.7
作者：
An F;Yamanaka S;Allen S;Roberts LR;Gores GJ;Pawlik TM;Xie Q;Ishida M;Mezey E;Ferguson-Smith AC;Mori Y;Selaru FM
通讯作者：
Selaru FM