Molecular Biotechnology Center (MBC), University of Torino, Torino, Italy.
EMBO J. 2011 May 18;30(10):1990-2007. doi: 10.1038/emboj.2011.102. Epub 2011 Apr 5.
Malignant melanoma is fatal in its metastatic stage. It is therefore essential to unravel the molecular mechanisms that govern disease progression to metastasis. MicroRNAs (miRs) are endogenous non-coding RNAs involved in tumourigenesis. Using a melanoma progression model, we identified a novel pathway controlled by miR-214 that coordinates metastatic capability. Pathway components include TFAP2C, homologue of a well-established melanoma tumour suppressor, the adhesion receptor ITGA3 and multiple surface molecules. Modulation of miR-214 influences in vitro tumour cell movement and survival to anoikis as well as extravasation from blood vessels and lung metastasis formation in vivo. Considering that miR-214 is known to be highly expressed in human melanomas, our data suggest a critical role for this miRNA in disease progression and the establishment of distant metastases.
恶性黑色素瘤在转移阶段是致命的。因此，揭示控制疾病进展转移的分子机制至关重要。MicroRNAs（miRs）是参与肿瘤发生的内源性非编码 RNA。我们使用黑色素瘤进展模型，鉴定出由 miR-214 控制的协调转移能力的新途径。途径组成部分包括 TFAP2C，已确立的黑色素瘤肿瘤抑制因子的同源物，黏附受体 ITGA3 和多个表面分子。miR-214 的调节会影响体外肿瘤细胞的运动和存活能力，以及对失巢凋亡的抵抗能力，以及血管外渗和体内肺转移的形成。考虑到 miR-214 在人类黑色素瘤中表达水平较高，我们的数据表明该 miRNA 在疾病进展和远处转移的建立中起着关键作用。
