MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression.
MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression.
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MiR-424-5p 通过直接靶向 ICAT 逆转不依赖贴壁的 HCC 细胞的上皮间质转化并抑制 HCC 进展
DOI：
10.1038/srep06248
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发表时间：
2014-09-01
影响因子：
4.6
通讯作者：
Han L
中科院分区：
文献类型：
--
作者：
Zhang Y;Li T;Guo P;Kang J;Wei Q;Jia X;Zhao W;Huai W;Qiu Y;Sun L;Han L
抗失巢凋亡和上皮-间质转化（EMT）是两个关键参与癌症转移的过程。本研究证明，肝细胞癌（HCC）细胞在锚定剥夺后不仅能抵抗失巢凋亡，而且还表现出EMT过程。微阵列表达谱显示miR-424- 5 p在失巢凋亡抵抗的HCC细胞中的表达显著降低。miR-424- 5 p的异位过表达可逆转肝癌细胞对失巢凋亡的抵抗，阻断EMT进程，抑制肝癌细胞的恶性行为。靶点分析表明，一种有效的β-catenin抑制剂ICAT/CTNNBIP 1是miR-424- 5 p的直接靶点。进一步的研究表明，miR-424- 5 p通过直接靶向ICAT并进一步维持E-cadherin/β-catanin复合物在细胞膜上的表达，逆转了肝癌细胞对失巢凋亡和EMT的抵抗。体内实验进一步证实miR-424- 5 p能显著抑制肝癌细胞在裸鼠体内的致瘤性。临床研究表明，miR-424- 5 p在肝癌组织中的表达明显低于癌旁肝组织，且与肝癌的病理分级和TNM分期密切相关。因此，miR-424- 5 p的异常表达与肝癌转移过程中的失巢凋亡和EMT抵抗密切相关，其下调显著促进肝癌进展。
Resistance to anoikis and Epithelial-mesenchymal transition (EMT) are two processes critically involved in cancer metastasis. In this study, we demonstrated that after anchorage deprival, hepatocellular carcinoma (HCC) cells not only resisted anoikis, but also exhibited EMT process. Microarray expression profiling revealed that expression of miR-424-5p was significantly decreased in anoikis-resistant HCC cells. Ectopic overexpression of miR-424-5p was sufficient to reverse resistance to anoikis, block EMT process and inhibit malignant behaviors of HCC cells. Target analysis showed that a potent β-catenin inhibitor, ICAT/CTNNBIP1 was a direct target of miR-424-5p. Further study demonstrated that miR-424-5p reversed resistance to anoikis and EMT of HCCs by directly targeting ICAT and further maintaining the E-cadherin/β-catanin complex on the cellular membrance. In vivo study further demonstrated that miR-424-5p significantly inhibited the tumorigenicity of HCC cells in nude mice. Clinical investigation demonstrated that miR-424-5p was significantly downregulated in HCC tissues compared with that of the non-cancerous liver tissues and this decreased expression of miR-424-5p was significantly correlated with higher pathological grades and more advanced TNM stages. Therefore, aberrant expression of miR-424-5p is critically involved in resistance to anoikis and EMT during the metastatic process of HCC and its downregulation significantly contributes to liver cancer progression.
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影响因子：
4.6
作者：
Banyard J;Chung I;Wilson AM;Vetter G;Le Béchec A;Bielenberg DR;Zetter BR
通讯作者：
Zetter BR
影响因子：
3.7
作者：
Oneyama C;Kito Y;Asai R;Ikeda J;Yoshida T;Okuzaki D;Kokuda R;Kakumoto K;Takayama K;Inoue S;Morii E;Okada M
通讯作者：
Okada M
影响因子：
28.5
作者：
Faraoni I;Laterza S;Ardiri D;Ciardi C;Fazi F;Lo-Coco F
通讯作者：
Lo-Coco F
DOI：
10.1073/pnas.0706963104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Rosa, A.;Ballarino, M.;Bozzoni, I.
通讯作者：
Bozzoni, I.
影响因子：
4.8
作者：
Nelson, Katja;Helmstaedter, Victor;Lage, Herrmann
通讯作者：
Lage, Herrmann