MicroRNA-574-5p was pivotal for TLR9 signaling enhanced tumor progression via down-regulating checkpoint suppressor 1 in human lung cancer.
MicroRNA-574-5p was pivotal for TLR9 signaling enhanced tumor progression via down-regulating checkpoint suppressor 1 in human lung cancer.
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MicroRNA-574-5p 在 TLR9 信号传导中通过下调人肺癌检查点抑制因子 1 增强肿瘤进展发挥关键作用。
DOI：
10.1371/journal.pone.0048278
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ren T
中科院分区：
文献类型：
--
作者：
Li Q;Li X;Guo Z;Xu F;Xia J;Liu Z;Ren T
越来越多的资料表明肿瘤细胞中Toll样受体（TLR）的功能性表达参与了肿瘤的进展。我们先前的研究表明，TLR9信号转导可以在体外和体内促进人肺癌细胞的肿瘤进展。我们进一步通过miRNA阵列分析表明，miR-574 - 5p是TLR9信号转导下人肺癌细胞中上调最多的miRNA。在这里，我们表征了miRNA-574 - 5p在人肺癌中由TLR9信号传导诱导的增强的肿瘤进展中的潜在作用。我们证实TLR9信号传导有效地提高了人肺癌细胞中miR-574 - 5p的表达。值得注意的是，我们发现在体外使用miR-574 - 5p抑制剂或在体内使用miR-574 - 5p海绵下调miRNA-574 - 5p显著消除了由TLR9信号传导诱导的增强的肿瘤进展。进一步的研究表明，miR-574 - 5p是与增强人肺癌细胞的肿瘤进展相关的重要参与者。值得注意的是，我们鉴定了检查点抑制因子1（Ches1）作为miRNA-574 - 5p的主要直接靶点，以赋予TLR9信号传导增强肿瘤进展。我们发现Ches 1的过表达显著抑制人肺癌细胞的细胞周期进入。肺癌组织中miR-574 - 5p的表达与TLR9呈正相关，miR-574 - 5p的表达与Ches 1呈正相关。我们的研究结果不仅有助于进一步理解肿瘤生物学中miRNA和TLR之间的串扰，而且还为癌症治疗提供了新的潜在候选者。
Accumulating data suggested that functional expression of Toll-like receptors (TLRs) in tumor cells was involved in tumor progression. Our previous study demonstrated that TLR9 signaling could enhance the tumor progression of human lung cancer cells in vitro and in vivo. We further showed that miR-574-5p was the mostly up-regulated miRNA in human lung cancer cells under TLR9 signaling by miRNA array analysis. Here we characterized the potential role of miRNA-574-5p in enhanced tumor progression induced by TLR9 signaling in human lung cancer. We confirmed that TLR9 signaling effectively elevated the expression of miR-574-5p in human lung cancer cells. Notably, we found that down-regulation of miRNA-574-5p using miR-574-5p inhibitor in vitro or miR-574-5p sponge in vivo significantly abrogated the enhanced tumor progression induced by TLR9 signaling. Further studies showed that miR-574-5p was an important player associated with enhanced tumor progression of human lung cancer cells. Notably, we identified checkpoint suppressor 1 (Ches1) as the dominant direct target for miRNA-574-5p to confer the TLR9 signaling enhanced tumor progression. We revealed that over-expression of Ches1 significantly inhibited the cell cycle entry of human lung cancer cells. Finally, we revealed that the expression of miR-574-5p was positively correlated with TLR9 and reversely correlated with Ches1 in lung cancer patients. Our findings not only facilitated the further understanding of the crosstalk between miRNAs and TLRs in tumor biology, but also provided novel potential candidates for treatment of cancer.