MicroRNA-124-3p inhibits cell migration and invasion in bladder cancer cells by targeting ROCK1.
MicroRNA-124-3p inhibits cell migration and invasion in bladder cancer cells by targeting ROCK1.
复制标题
DOI：
10.1186/1479-5876-11-276
复制
发表时间：
2013-11-02
影响因子：
7.4
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Xu X;Li S;Lin Y;Chen H;Hu Z;Mao Y;Xu X;Wu J;Zhu Y;Zheng X;Luo J;Xie L
越来越多的证据表明，某些微小RNA（microRNAs，miRNAs）的表达异常可能与人类疾病的发生、发展和转移有关。miR-124- 3 p在多种癌症中下调，并调节癌细胞的增殖和侵袭性。然而，miR-124- 3 p在人膀胱癌中的作用是难以捉摸的。因此，本研究旨在探讨miR-124- 3 p在人膀胱癌细胞系中的生物学功能及其分子机制，探讨其是否有潜力成为膀胱癌的治疗性生物标志物。通过定量RT-PCR分析了三种人膀胱癌细胞系和十名膀胱癌患者的样本中miR-124- 3 p的表达。将模拟物转染T24、UM-UC-3和J82细胞，建立miR-124- 3 p的外源性过表达模型，通过MTT法、流式细胞术和集落形成实验检测细胞增殖和细胞周期。创伤愈合实验和transwell实验检测细胞运动和侵袭能力。采用过氧化物酶法和DAB法进行组织芯片和ROCK 1、MMP 2和MMP 9抗体免疫组化。通过荧光素酶检测、定量RT-PCR和western blot检测miR-124- 3 p的靶基因。通过western blot分析miR-124- 3 p对上皮向间质转化的调节。miR-124- 3 p在三种膀胱癌细胞系T24、UM-UC-3、J82和临床样品中在膀胱癌中频繁下调。miR-124- 3 p过表达可诱导T24、UM-UC-3和J82细胞G1期阻滞，并抑制细胞集落形成。miR-124- 3 p显著抑制膀胱癌细胞的迁移和侵袭能力。此外，ROCK 1被鉴定为miR-124- 3 p的新靶点。ROCK 1、MMP 2、MMP 9在膀胱癌组织中表达上调。miR-124- 3 p能够抑制膀胱癌细胞间质转移，并调控c-Met、MMP 2、MMP 9的表达。miR-124- 3 p可通过调控ROCK 1抑制膀胱癌细胞的迁移和侵袭。我们的数据表明，miR-124- 3 p可能是一种肿瘤抑制因子，并可能成为膀胱癌的诊断或预测生物标志物。
Increasing evidence has suggested that dysregulation of certain microRNAs (miRNAs) may contribute to human disease including carcinogenesis and tumor metastasis in human. miR-124-3p is down-regulated in various cancers, and modulates proliferation and aggressiveness of cancer cells. However, the roles of miR-124-3p in human bladder cancer are elusive. Thus, this study was conducted to investigate the biological functions and its molecular mechanisms of miR-124-3p in human bladder cancer cell lines, discussing whether it has a potential to be a therapeutic biomarker of bladder cancer. Three human bladder cancer cell lines and samples from ten patients with bladder cancer were analyzed for the expression of miR-124-3p by quantitative RT--PCR. Exogenetic overexpression of miR-124-3p was established by transfecting mimics into T24, UM-UC-3 and J82 cells, after that cell proliferation and cell cycle were assessed by MTT assay, flow cytometry and Colony-forming assay. Cell motility and invasion ability were evaluated by wound healing assay and transwell assay. Tissue microarray, and immunohistochemistry with antibodies against ROCK1, MMP2 and MMP9 was performed using the peroxidase and DAB methods. The target gene of miR-124-3p was determined by luciferase assays, quantitative RT--PCR and western blot. The regulation of epithelial-to-mesenchymal transition by miR-124-3p was analyzed by western blot. miR-124-3p is frequently down-regulated in bladder cancer both in three bladder cancer cell lines, T24, UM-UC-3, J82 and clinical samples. Overexpression of miR-124-3p induced G1-phase arrest in T24, UM-UC-3 and J82 cell lines and suppressed cell growth in colony-forming assay. miR-124-3p significantly repressed the capability of migration and invasion of bladder cancer cells. In addition, ROCK1 was identified as a new target of miR-124-3p. ROCK1, MMP2, MMP9 were up-regulated in bladder cancer tissues. Furthermore, we demonstrated miR-124-3p could inhibit bladder cancer cell epithelial mesenchymal transfer, and regulated the expression of c-Met, MMP2, MMP9. miR-124-3p can repress the migration and invasion of bladder cancer cells via regulating ROCK1. Our data indicate that miR-124-3p could be a tumor suppressor and may have a potential to be a diagnostics or predictive biomarker in bladder cancer.
登录
查看更多内容
影响因子：
3.5
作者：
Hunt, Stuart;Jones, Adam V.;Lambert, Daniel W.
通讯作者：
Lambert, Daniel W.
酪氨酸激酶 c-Met 有助于人胆管胆管癌细胞中 p38 激酶的促肿瘤功能
影响因子：
4.8
作者：
Dai, Rongyang;Li, Juanjuan;Wang, Hongyang
通讯作者：
Wang, Hongyang
DOI：
10.1016/j.biocel.2007.07.011
发表时间：
2007-01-01
影响因子：
4
作者：
Guarino, Marcello
通讯作者：
Guarino, Marcello
N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
影响因子：
2.4
作者：
Kakehi, Yoshiyuki;Hirao, Yoshihiko;Yokomizo, Akira
通讯作者：
Yokomizo, Akira