Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Medical Genetics, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cancer Epidemiol. 2014 Feb;38(1):85-92. doi: 10.1016/j.canep.2013.12.005. Epub 2014 Jan 17.
The miR-451 was found to be frequently down-regulated in tumors, indicating that miR-451 could play an important role in carcinogenesis. This study uncovered the mechanism by which the miR-451 functions as a tumor suppressor. The target genes of miR-451 were determined using target gene prediction softwares. Then the miR-451 mimics were introduced into RKO and Hela cells respectively. The proliferation and invasion of cells were monitored by MTT, cell cycle and in vitro extracellular matrix invasion assays. Also the angiogenesis of HUVEC cells transfected with miR-451 mimics was examined. Subsequently, IL6R, a predicted target gene of miR-451, was studied by real time PCR, Western blotting, and siRNA technologies. The mRNA and protein levels of IL6R gene were found to be down-regulated in the RKO and Hela cells transfected with miR-451 mimics. Consequently, the cell proliferation was inhibited. Also, the invasion of RKO cells was suppressed. Furthermore, the angiogenesis of HUVEC cells transfected with miR-451 mimics was assayed and the decreased angiogenic ability was detected compared to the controls. All these results were validated by IL6R siRNA experiments. The IL6R gene is a target gene of miR-451. The miR-451 behaves as a tumor suppressor, probably by targeting the IL6R pathway.
miR-451 在肿瘤中经常下调，表明 miR-451 可能在肿瘤发生中发挥重要作用。本研究揭示了 miR-451 作为肿瘤抑制因子的作用机制。使用靶基因预测软件确定了 miR-451 的靶基因。然后将 miR-451 模拟物分别引入 RKO 和 Hela 细胞。通过 MTT、细胞周期和体外细胞外基质侵袭测定监测细胞的增殖和侵袭。还检测了转染 miR-451 模拟物的 HUVEC 细胞的血管生成。随后，通过实时 PCR、Western blot 和 siRNA 技术研究了 IL6R，这是 miR-451 的一个预测靶基因。发现在转染 miR-451 模拟物的 RKO 和 Hela 细胞中，IL6R 基因的 mRNA 和蛋白水平下调。因此，细胞增殖受到抑制。此外，RKO 细胞的侵袭也受到抑制。此外，还检测了转染 miR-451 模拟物的 HUVEC 细胞的血管生成，与对照组相比，检测到血管生成能力下降。所有这些结果都通过 IL6R siRNA 实验得到验证。IL6R 基因是 miR-451 的靶基因。miR-451 作为肿瘤抑制因子，可能通过靶向 IL6R 途径发挥作用。
