Regulation of RPTPα-c-Src signalling pathway by miR-218
Regulation of RPTPα-c-Src signalling pathway by miR-218
复制标题
miR-218 调节 RPTPα-c-Src 信号通路
DOI：
10.1111/febs.13314
复制
发表时间：
2015-07-01
期刊：
影响因子：
5.4
通讯作者：
Huang, Jian
中科院分区：
文献类型：
--
作者：
Lai, Xueping;Chen, Qin;Huang, Jian
受体蛋白酪氨酸磷酸酶 α (RPTP α) 是 Src 家族激酶的激活剂，被发现在人类癌症组织中显着过度表达。然而，人们对 RPTP α 表达的调节知之甚少。 miRNA 靶向多个基因并在许多癌症过程中发挥重要作用。在这里，我们鉴定了一种 miRNA，miR-218，它直接与 RPTP α 的 30-UTR 结合。 miR-218 的异位过度表达降低了 RPTP α 蛋白，导致 c-Src 去磷酸化减少，并减少体外和体内肿瘤生长。揭示了 c-Src 和 miR-218 之间的反馈环路，其中 c-Src 抑制 SLIT2 的转录，而 SLIT2 是 miR-218 的内含子宿主。这些结果显示了 RPTP α-c-Src 信号传导的新调控途径。
Receptor protein tyrosine phosphatase alpha (RPTP alpha), an activator of Src family kinases, is found significantly overexpressed in human cancer tissues. However, little is known about the regulation of RPTP alpha expression. miRNAs target multiple genes and play important roles in many cancer processes. Here, we identified a miRNA, miR-218 that binds directly to the 30-UTR of RPTP alpha. Ectopic overexpression of miR-218 decreased RPTP alpha protein leading to decreased dephosphorylation of c-Src and decreased tumour growth in vitro and in vivo. A feedback loop between c-Src and miR-218 was revealed where c-Src inhibits transcription of SLIT2, which intronically hosts miR-218. These results show a novel regulatory pathway for RPTP alpha-c-Src signalling.