Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer.
Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer.
复制标题
DOI：
10.1111/cas.12441
复制
发表时间：
2014-07
期刊：
影响因子：
5.7
通讯作者：
Seki N
中科院分区：
文献类型：
--
作者：
Nishikawa R;Goto Y;Sakamoto S;Chiyomaru T;Enokida H;Kojima S;Kinoshita T;Yamamoto N;Nakagawa M;Naya Y;Ichikawa T;Seki N
我们最近对前列腺癌（PCa）中microRNA（miRNA）表达特征的研究表明，miRNA-218（miR-218）在临床标本中显著下调，这表明miR-218可能在PCa中起肿瘤抑制性miRNA的作用。本研究的目的是研究miR-218在PCa中的功能意义，并确定新的miR-218调控的癌症途径和参与PCa肿瘤发生和转移的靶基因。miR-218在PCa细胞系（PC 3和DU 145）中的恢复显示，该miRNA显著抑制癌细胞的迁移和侵袭。基因表达数据和计算机模拟分析表明，LIM和SH 3蛋白1（LASP 1）是miR-218调控的潜在靶点。LASP 1是一种细胞骨架支架蛋白，在细胞骨架组织和细胞迁移中起关键作用。荧光素酶报告基因测定表明，miR-218直接调节LASP 1的表达。此外，下调LASP 1基因显著抑制癌细胞的细胞迁移和侵袭，并且LASP 1在癌组织中的表达上调。我们得出结论，肿瘤抑制miR-218的丢失通过直接调节LASP 1增强了PCa中癌细胞的迁移和侵袭。我们关于肿瘤抑制性miR-218调控途径的数据为PCa肿瘤发生和转移的潜在机制提供了新的见解。
Our recent studies of the microRNA (miRNA) expression signature in prostate cancer (PCa) indicated that miRNA-218 (miR-218) was significantly downregulated in clinical specimens, suggesting that miR-218 might act as a tumor-suppressive miRNA in PCa. The aim of the present study was to investigate the functional significance of miR-218 in PCa and to identify novel miR-218-regulated cancer pathways and target genes involved in PCa oncogenesis and metastasis. Restoration of miR-218 in PCa cell lines (PC3 and DU145) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that LIM and SH3 protein 1 (LASP1) is a potential target of miR-218 regulation. LASP1 is a cytoskeletal scaffold protein that plays critical roles in cytoskeletal organization and cell migration. Luciferase reporter assays showed that miR-218 directly regulated expression of LASP1. Moreover, downregulating the LASP1 gene significantly inhibited cell migration and invasion in cancer cells, and the expression of LASP1 was upregulated in cancer tissues. We conclude that loss of tumor-suppressive miR-218 enhanced cancer cell migration and invasion in PCa through direct regulation of LASP1. Our data on pathways regulated by tumor-suppressive miR-218 provide new insight into the potential mechanisms of PCa oncogenesis and metastasis.
登录
查看更多内容
MiR-218通过靶向Robo1受体抑制胃癌的侵袭和转移。
影响因子：
4.5
作者：
Tie J;Pan Y;Zhao L;Wu K;Liu J;Sun S;Guo X;Wang B;Gang Y;Zhang Y;Li Q;Qiao T;Zhao Q;Nie Y;Fan D
通讯作者：
Fan D
LASP-1 的过度表达介导人卵巢癌细胞的迁移和增殖并影响 zyxin 定位。
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
8.8
作者：
Kojima, S.;Chiyomaru, T.;Kawakami, K.;Yoshino, H.;Enokida, H.;Nohata, N.;Fuse, M.;Ichikawa, T.;Naya, Y.;Nakagawa, M.;Seki, N.
通讯作者：
Seki, N.
影响因子：
3.3
作者：
Mori, Masaki;Nakagami, Hironori;Kaneda, Yasufumi
通讯作者：
Kaneda, Yasufumi
影响因子：
8.8
作者：
通讯作者：
--