miR-214 promotes tumorigenesis by targeting lactotransferrin in nasopharyngeal carcinoma
miR-214 promotes tumorigenesis by targeting lactotransferrin in nasopharyngeal carcinoma
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miR-214通过靶向乳转铁蛋白促进鼻咽癌肿瘤发生
DOI：
10.1007/s13277-013-0718-y
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发表时间：
2013-06-01
期刊：
影响因子：
--
通讯作者：
Li, Guiyuan
中科院分区：
文献类型：
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作者：
Deng, Min;Ye, Qiurong;Li, Guiyuan
乳转铁蛋白（lactotransferrin，LTF）在天然免疫中起重要作用，其抗肿瘤作用在多种肿瘤中也有报道。我们以前报道，LTF在鼻咽癌（NPC）中显著下调，并通过抑制AKT信号转导作为肿瘤抑制因子。然而，LTF在NPC中下调的确切机制尚未被揭示。在本研究中，我们筛选并鉴定了LTF是miR-214在NPC细胞中的真正靶点。miR-214模拟物显著抑制NPC细胞中LTF mRNA和蛋白表达水平。miR-214不仅在体外能促进鼻咽癌细胞的增殖和侵袭能力，而且在小鼠异种移植模型中能加速肿瘤的形成和肺转移。miR-214的促肿瘤作用依赖于LTF的抑制，因为LTF的再表达可以逆转它。miR-214还可以通过抑制LTF的表达来激活AKT信号传导。此外，与正常鼻咽上皮组织相比，miR-214在NPC中表达上调，尤其是在转移倾向性NPC肿瘤组织中，而LTF表达水平与miR-214呈负相关，提示miR-214靶向可能是NPC标本中LTF下调的部分原因。
LTF (lactotransferrin, or lactoferrin) plays important role in innate immunity, and its anti-tumor function has also been reported in multiple cancers. We previously reported that LTF is significantly down-regulated in nasopharyngeal carcinoma (NPC) and acts as a tumor suppressor by suppressing AKT signaling. However, the exact mechanism of the down-regulation of LTF in NPC has not been revealed. In the current study, we screened and identified LTF is a bona fide target of miR-214 in NPC cells. miR-214 mimics significantly suppressed LTF mRNA and protein expression levels in NPC cells. miR-214 not only can promote NPC cell proliferation and invasion abilities in vitro, but also can accelerate tumor formation and lung metastasis in a mouse xenograft model. The pro-tumor function of miR-214 was depended on LTF suppression since LTF re-expression can reverse it. miR-214 can also activate AKT signaling by suppressing LTF expression. Furthermore, miR-214 expression level was up-regulated in NPC especially in metastasis-prone NPC tumor tissues compared with normal nasopharyngeal epithelial tissues, while the LTF expression level was negatively correlated with miR-214, suggesting that miR-214 targeting is partly responsible for LTF down-regulation in NPC specimens.