microRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4
microRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4
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microRNA-499-5p通过靶向FOXO4和PDCD4促进结直肠癌细胞侵袭和肿瘤转移
DOI：
10.1093/carcin/bgr213
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发表时间：
2011-12-01
期刊：
影响因子：
4.7
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Liu, Xiangqiang;Zhang, Zhiyong;Fan, Daiming
MicroRNAs(MiRNAs)通过与靶信使RNAs(MRNAs)直接相互作用来调控肿瘤的进展和侵袭。我们使用已建立的结肠腺癌最低转移细胞(SW480株)和1年后同一患者转移淋巴结高转移细胞(SW620株)的体外模型，定义了与癌症转移(转移)有关的miRNAs。我们利用微阵列技术分析了在SW480和SW620细胞中差异表达的miRNA，重点研究了miR-499-5p作为一种新的前转移候选miRNA，其在癌症中的功能尚未被研究。我们证实在高侵袭性的CRC细胞系和淋巴结阳性的CRC标本中miR-499-5p水平增加。此外，上调miR-499-5p的表达可促进结直肠癌细胞的体外迁移和侵袭以及体内肺和肝转移，而沉默miR-499-5p的表达则可减少其迁移和侵袭。此外，我们确定FOXO4和PDCD4是miR-499-5p的直接和功能靶点。综上所述，这些发现提示miR-499-5p促进了结直肠癌细胞的转移，可能成为结直肠癌治疗的新的潜在靶点。
MicroRNAs (miRNAs) regulate tumor progression and invasion via direct interaction with target messenger RNAs (mRNAs). We defined miRNAs involved in cancer metastasis (metastamirs) using an established in vitro colorectal cancer (CRC) model of minimally metastatic cells (SW480 line) from a colon adenocarcinoma primary lesion and highly metastatic cells (SW620 line) from a metastatic lymph node from the same patient 1 year later. We used microarray analysis to identify miRNAs differentially expressed in SW480 and SW620 cells, focusing on miR-499-5p as a novel candidate prometastatic miRNA whose functions in cancer had not been studied. We confirmed increased miR-499-5p levels in highly invasive CRC cell lines and lymph node-positive CRC specimens. Furthermore, enhancing the expression of miR-499-5p promoted CRC cell migration and invasion in vitro and lung and liver metastasis in vivo, while silencing its expression resulted in reduced migration and invasion. Additionally, we identified FOXO4 and PDCD4 as direct and functional targets of miR-499-5p. Collectively, these findings suggested that miR-499-5p promoted metastasis of CRC cells and may be useful as a new potential therapeutic target for CRC.