Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway.
Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway.
复制标题
DOI：
10.18632/oncotarget.2880
复制
发表时间：
2015-02-28
期刊：
影响因子：
--
通讯作者：
Wen X
中科院分区：
文献类型：
--
作者：
Cai S;Chen R;Li X;Cai Y;Ye Z;Li S;Li J;Huang H;Peng S;Wang J;Tao Y;Huang H;Wen X;Mo J;Deng Z;Wang J;Zhang Y;Gao X;Wen X
在这里，我们发现miR-23 a的水平在前列腺癌细胞系和肿瘤组织中降低。这些低水平与患者预后不良有关。miR-23 a在体内和原位前列腺癌小鼠模型中抑制前列腺癌的迁移和侵袭。miR-23 a降低p21激活的激酶6（PAK 6）的水平。miR-23 a的表达抑制了LIM激酶1（LIMK 1）和cofilin的磷酸化，进而抑制了细胞运动和侵袭所需的应力纤维和肌动蛋白丝的形成。PAK 6与LIMK 1结合并通过Thr-508磷酸化激活LIMK 1。此外，PAK 6和LIMK 1共定位于细胞质中。因此，miR-23 a通过影响LIMK 1和cofilin来调节细胞骨架。总之，我们已经确定了前列腺癌转移的miR-23 a-PAK 6-LIMK 1通路。提出了靶向miR-23的潜在治疗方法。
Here we found that levels of miR-23a were decreased in prostate cancer cell lines and tumor tissues. These low levels were associated with poor patients' prognosis. MiR-23a inhibited migration and invasion of prostate cancer in vivo and in orthotopic prostate cancer mice model. MiR-23a decreased levels of p21-activated kinase 6 (PAK6). Expression of miR-23a inhibited phosphorylation of LIM kinase 1 (LIMK1) and cofilin, in turn suppressing formation of stress fibers and actin filaments, which was required for cell motility and invasion. PAK6 bound to LIMK1 and activated it via phosphorylation at Thr-508. Also, PAK6 and LIMK1 were colocalized in the cytoplasma. Thus, miR-23a regulated cytoskeleton by affecting LIMK1 and cofilin. In summary, we have identified the miR-23a-PAK6-LIMK1 pathway of prostate cancer metastasis. Potential therapeutic approach by targeting miR-23 is suggested.
登录
查看更多内容
影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
6.4
作者：
Huang, Shenglin;He, Xianghuo;Gu, Jianren
通讯作者：
Gu, Jianren
影响因子：
--
作者：
Kinoshita T;Hanazawa T;Nohata N;Kikkawa N;Enokida H;Yoshino H;Yamasaki T;Hidaka H;Nakagawa M;Okamoto Y;Seki N
通讯作者：
Seki N
影响因子：
2.9
作者：
Cheng L;Yang T;Kuang Y;Kong B;Yu S;Shu H;Zhou H;Gu J
通讯作者：
Gu J
影响因子：
56.9
作者：
Ghosh, M;Song, XY;Condeelis, JS
通讯作者：
Condeelis, JS