Identification of micro RNAs which affected by tumor microenvironments of ovarian cancer and analysis of a potential as a therapeutic target

在卵巢癌细胞扩散过程中，细胞漂浮在腹膜腔内，没有血管供应，暴露在缺氧条件下。我们认为缺氧刺激影响卵巢癌细胞的行为。在这项研究中，我们筛选了在缺氧条件下表达改变的mirna。miRNA PCR结果显示，缺氧条件下miR-199a-3p的表达降低。计算机分析使我们认为MET是miR-199a-3p的靶基因之一。在卵巢癌细胞中miR-199a-3p的表达与c-Met的表达呈负相关。将前体miR-199a-3p转染到卵巢癌细胞中，降低c-Met的表达，抑制其增殖、粘附和侵袭。在卵巢癌异种移植模型中，SKOV3细胞中miR-199a-3p的强制表达显著抑制了腹膜播散。因此，我们认为miR-199a-3p是治疗卵巢癌传播的潜在靶点。

During the dissemination of ovarian cancer cells, cells are floating in the peritoneal cavity without vascular supply and exposed in hypoxic conditions. We suggest that hypoxic stimuli affect ovarian cancer cell behavior. In this study, we screened miRNAs which expression were altered under hypoxic condition. miRNA PCR arrays revealed that the expression of miR-199a-3p decreased under hypoxic conditions. In silico analyses led us to consider MET is one of the target genes of miR-199a-3p. miR-199a-3p expression was inversely correlated with c-Met expression in ovarian cancer cells. Transfection of precursor miR-199a-3p into ovarian cancer cells reduced c-Met expression followed by the inhibition of the proliferation, adhesion and invasion. In an ovarian cancer xenograft model, the enforced expression of miR-199a-3p in SKOV3 cells significantly suppressed peritoneal dissemination. Thus we suggested that miR-199a-3p is a potential target for treating ovarian cancer dissemination.