Snail-regulated MiR-375 inhibits migration and invasion of gastric cancer cells by targeting JAK2.

Snail-regulated MiR-375 inhibits migration and invasion of gastric cancer cells by targeting JAK2.
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蜗牛调控的 MiR-375 通过靶向 JAK2 抑制胃癌细胞的迁移和侵袭

DOI:
10.1371/journal.pone.0099516
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Zhuo W
Zhuo W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Xu Y;Jin J;Liu Y;Huang Z;Deng Y;You T;Zhou T;Si J;Zhuo W

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据报道,微小RNA(miRNA)在癌症侵袭和转移中发挥着关键作用。我们之前的研究表明,miR-375 在胃癌中频繁下调,通过靶向 Janus 激酶 2 (JAK2) 抑制细胞增殖。在这里,我们进一步发现,与非转移对照相比,转移性胃癌组织中miR-375的表达水平显着降低。 miR-375的异位表达部分通过靶向JAK2抑制胃癌细胞的迁移和侵袭。此外,miR-375 的表达受到转移相关转录因子 Snail 的负向调节,Snail 直接与 miR-375 的推定启动子结合。此外,Snail的过表达可以部分逆转miR-375对胃癌细胞迁移的抑制。综上所述,这些数据表明 miR-375 可能受到 Snail 的负向调节,并可能通过靶向 JAK2 参与胃癌细胞的迁移和侵袭。
MicroRNAs (miRNAs) have been reported to play a critical role in cancer invasion and metastasis. Our previous study showed that miR-375 frequently downregulated in gastric cancer suppresses cell proliferation by targeting Janus kinase 2 (JAK2). Here, we further found that the expression level of miR-375 is significantly decreased in metastatic gastric cancer tissues compared with the non-metastasis controls. Ectopic expression of miR-375 inhibits the migration and invasion of gastric cancer cells partially by targeting JAK2. Furthermore, miR-375 expression is negatively regulated by the metastasis associated transcription factor Snail, which directly binds to the putative promoter of miR-375. Moreover, overexpression of Snail can partially reverse the inhibition of gastric cancer cell migration caused by miR-375. Taken together, these data suggest that miR-375 may be negatively regulated by Snail and involved in gastric cancer cell migration and invasion potentially by targeting JAK2.
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