Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma.
Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma.
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DOI：
10.1002/ijc.25320
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发表时间：
2010-08-01
影响因子：
6.4
通讯作者：
Zhou, Xiaofeng
中科院分区：
文献类型：
--
作者：
Jiang, Lu;Liu, Xiqiang;Kolokythas, Antonia;Yu, Jinsheng;Wang, Anxun;Heidbreder, Caroline E.;Shi, Fei;Zhou, Xiaofeng
肿瘤转移是癌症患者（包括口腔舌鳞状细胞癌（TSCC）患者）死亡的主要原因。先前，我们报道了miR-138水平降低与TSCC细胞中转移潜能增强相关。在这里，我们证明了miR-138通过调节Rho GT3信号通路中的两个关键基因：RhoC和ROCK 2来抑制TSCC细胞的迁移和侵袭。使用荧光素酶报告基因测定证实miR-138直接靶向位于RhoC和ROCK 2 mRNA的3′-非翻译区的特定序列。miR-138的异位转染降低了TSCC细胞中RhoC和ROCK 2的表达。结果，这些减少的表达导致应力纤维的重组和随后的细胞形态改变为圆形水泡样形状，以及细胞迁移和侵袭的抑制。相反，TSCC细胞中miR-138的敲低增强了RhoC和ROCK 2的表达，这导致细胞形态改变，延长，增强细胞应力纤维形成，并加速细胞迁移和侵袭。综上所述，我们的研究结果表明，miR-138通过同时靶向RhoC和ROCK 2在TSCC细胞迁移和侵袭中起重要作用，miR-138可作为TSCC患者转移性疾病风险的新治疗靶点。
Tumor metastasis is the dominant cause of death in cancer patients, including patients with oral tongue squamous cell carcinoma (TSCC). Previously, we reported that reduced miR-138 level is correlated with enhanced metastatic potential in TSCC cells. Here, we demonstrate that miR-138 suppresses TSCC cell migration and invasion by regulating two key genes in the Rho GTPase signaling pathway: RhoC and ROCK2. Direct targeting of miR-138 to specific sequences located in the 3′-untranslated regions of both RhoC and ROCK2 mRNAs were confirmed using luciferase reporter gene assays. Ectopic transfection of miR-138 reduced the expression of both RhoC and ROCK2 in TSCC cells. These reduced expressions, in consequence, led to the reorganization of the stress fibers and the subsequent cell morphology change to a round bleb-like shape, as well as the suppression of cell migration and invasion. In contrast, knockdown of miR-138 in TSCC cells enhanced the expression of RhoC and ROCK2, which resulted in an altered, elongated cell morphology, enhanced cell stress fiber formation, and accelerated cell migration and invasion. Taken together, our results suggest that miR-138 plays an important role in TSCC cell migration and invasion by concurrently targeting RhoC and ROCK2, and miR-138 may serve as a novel therapeutic target for TSCC patients at risk of metastatic disease.
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影响因子：
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作者：
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