Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Acta Biochim Biophys Sin (Shanghai). 2012 May;44(5):407-14. doi: 10.1093/abbs/gms019. Epub 2012 Apr 2.
MicroRNAs are important gene regulators that play a profound role in tumorigenesis. MicroRNA-145 (miR-145), an important member in the family of microRNAs, is under-expressed in several types of tumors and acts as a tumor suppressor. The role and probable pathways of miR-145 in osteosarcoma carcinogenesis are still unknown. In this study, we found that miR-145 was significantly under-expressed in osteosarcoma tissues, and the over-expression of miR-145 could inhibit invasion and angiopoiesis of osteosarcoma cells. Furthermore, the results showed that vascular endothelial growth factor (VEGF) expression was down-regulated in osteosarcoma cells after miR-145 transfection. On the basis of these results, we performed the luciferase assay and verified that miR-145 could down-regulate VEGF at the translational level by partially binding to VEGF 3' untranslated region (3'UTR). Therefore, it can be concluded that miR-145 can inhibit invasion and metastasis of osteosarcoma cells. One of the mechanisms is the down-regulation of VEGF expression by miR-145 by binding to the 3'UTR of VEGF mRNA specifically. These novel findings may have extensive implications for an effective gene therapy of osteosarcoma.
微小 RNA 是重要的基因调控因子，在肿瘤发生中发挥着深远的作用。微小 RNA-145（miR-145）是微小 RNA 家族中的一个重要成员，在几种类型的肿瘤中表达下调，作为肿瘤抑制因子发挥作用。miR-145 在骨肉瘤发生中的作用和可能的途径尚不清楚。在本研究中，我们发现 miR-145 在骨肉瘤组织中显著下调，miR-145 的过表达可抑制骨肉瘤细胞的侵袭和血管生成。此外，研究结果表明，miR-145 转染后骨肉瘤细胞中血管内皮生长因子（VEGF）的表达下调。基于这些结果，我们进行了荧光素酶测定，并验证了 miR-145 可以通过与 VEGF 3'非翻译区（3'UTR）的部分结合来在翻译水平下调 VEGF。因此，可以得出结论，miR-145 可以抑制骨肉瘤细胞的侵袭和转移。其中一种机制是 miR-145 通过与 VEGF mRNA 的 3'UTR 特异性结合来下调 VEGF 的表达。这些新发现可能对骨肉瘤的有效基因治疗具有广泛的意义。
