miR-143 and miR-145 inhibit gastric cancer cell migration and metastasis by suppressing MYO6.
miR-143 and miR-145 inhibit gastric cancer cell migration and metastasis by suppressing MYO6.
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miR-143和miR-145通过抑制MYO6抑制胃癌细胞迁移和转移
DOI：
10.1038/cddis.2017.493
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发表时间：
2017-10-12
影响因子：
9
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Lei C;Du F;Sun L;Li T;Li T;Min Y;Nie A;Wang X;Geng L;Lu Y;Zhao X;Shi Y;Fan D
转移是导致胃癌死亡率高、预后差的主要临床障碍。微小RNA（miRNAs）是转移的关键介质，其通过调节其靶基因起作用。在这项研究中，我们发现miR-143和miR-145通过共同的靶基因MYO 6来调节上皮-间质转化（EMT）并抑制转移。我们确定miR-143和miR-145在GC中下调，并且miR-143和/或miR-145的异位表达抑制GC细胞的迁移和转移。此外，MYO 6被鉴定为miR-143和miR-145的直接共同靶点，并且在GC中升高。沉默MYO 6导致与miR-143和miR-145相似的转移抑制活性，而恢复MYO 6减弱了由miR-143和miR-145引起的抗转移或抗EMT作用。临床上，胃癌组织中miR-143/145水平与MYO 6水平呈负相关，miR-143/145下调或MYO 6上调与胃癌患者的恶性表型相关。综上所述，miR-143和miR-145通过抑制MYO 6的表达和EMT抑制胃癌细胞的迁移和转移，为胃癌转移的治疗提供了新的机制和有前景的治疗靶点。
Metastasis is a major clinical obstacle responsible for the high mortality and poor prognosis of gastric cancer (GC). MicroRNAs (miRNAs) are critical mediators of metastasis that act by modulating their target genes. In this study, we found that miR-143 and miR-145 act via a common target gene, MYO6, to regulate the epithelial–mesenchymal transition (EMT) and inhibit metastasis. We determined that miR-143 and miR-145 were downregulated in GC, and the ectopic expression of miR-143 and/or miR-145 inhibited GC cell migration and metastasis. Furthermore, MYO6 was identified as a direct common target of miR-143 and miR-145 and was elevated in GC. Silencing of MYO6 resulted in a metastasis-suppressive activity similar to that of miR-143 and miR-145, while restoring MYO6 attenuated the anti-metastatic or anti-EMT effects caused by miR-143 and miR-145. Clinically, an inverse correlation was observed between miR-143/145 levels and MYO6 levels in GC tissues, and either miR-143/145 downregulation or MYO6 upregulation was associated with more malignant phenotypes in patients with GC. In conclusion, miR-143 and miR-145 suppress GC cell migration and metastasis by inhibiting MYO6 expression and the EMT, which provides a novel mechanism and promising therapeutic target for the treatment of GC metastasis.
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影响因子：
28.2
作者：
Dimitrova N;Gocheva V;Bhutkar A;Resnick R;Jong RM;Miller KM;Bendor J;Jacks T
通讯作者：
Jacks T
影响因子：
3.7
作者：
Hu J;Guo H;Li H;Liu Y;Liu J;Chen L;Zhang J;Zhang N
通讯作者：
Zhang N
MiR-145 调节肺腺癌起始细胞的癌症干细胞样特性和上皮间质转化
影响因子：
--
作者：
Hu, Jingwen;Qiu, Mantang;Yin, Rong
通讯作者：
Yin, Rong
影响因子：
82.9
作者：
Bonci, Desiree;Coppola, Valeria;De Maria, Ruggero
通讯作者：
De Maria, Ruggero
影响因子：
4.2
作者：
Huang, Shuak;Guo, Wei;Peng, Xinsheng
通讯作者：
Peng, Xinsheng