State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.
J Cell Mol Med. 2011 Sep;15(9):1887-95. doi: 10.1111/j.1582-4934.2010.01194.x.
MicroRNAs are small non-coding RNA molecules that control expression of target genes. Previous studies showed that microRNA-107 (miR-107) is overexpressed in gastric cancer tissues compared with the matched normal tissues. However, it remains largely unclear as to how miR-107 exerts its function and modulates the malignant phenotypes of gastric cancer, because our understanding of miR-107 signalling pathways is limited. In this study, we demonstrate that miR-107 is frequently up-regulated in gastric cancers and its overexpression is significantly associated with gastric cancer metastasis. Furthermore, silencing the expression of miR-107 could inhibit gastric cancer cell migration and invasion in vitro and in vivo. Subsequent investigation characterized DICER1 as a direct target of miR-107. Up-regulation of DICER1 resulted in a dramatic reduction of in vitro migration, invasion, in vivo liver metastasis of nude mice, which is similar to that occurs with the silencing of miR-107, indicating that DICER1 functions as a metastasis suppressor in gastric cancer. Furthermore, the restoration of DICER1 can inhibit miR-107-induced gastric cancer cell invasion and metastasis. In conclusion, our results suggested that miR-107, an oncogene miRNA promoting gastric cancer metastasis through down-regulation of DICER1. Inhibition of miR-107 or restoration of DICER1 may represent a new potential therapeutic target for gastric cancer treatment.
微小 RNA 是一种控制靶基因表达的小型非编码 RNA 分子。先前的研究表明,与匹配的正常组织相比,胃癌组织中 microRNA-107(miR-107)表达过度。然而,miR-107 如何发挥其功能并调节胃癌的恶性表型在很大程度上仍不清楚,因为我们对 miR-107 信号通路的理解有限。在这项研究中,我们证明 miR-107 在胃癌中经常上调,其过表达与胃癌转移显著相关。此外,沉默 miR-107 的表达可抑制体外和体内胃癌细胞的迁移和侵袭。随后的研究表明 DICER1 是 miR-107 的直接靶标。DICER1 的上调导致体外迁移、侵袭明显减少,裸鼠体内肝转移也类似,与 miR-107 的沉默相似,表明 DICER1 在胃癌中作为转移抑制因子发挥作用。此外,DICER1 的恢复可以抑制 miR-107 诱导的胃癌细胞侵袭和转移。总之,我们的研究结果表明,miR-107 是一种致癌 miRNA,通过下调 DICER1 促进胃癌转移。抑制 miR-107 或恢复 DICER1 可能代表胃癌治疗的一个新的潜在治疗靶点。