TLR9 signaling repressed tumor suppressor miR-7 expression through up-regulation of HuR in human lung cancer cells.
TLR9 signaling repressed tumor suppressor miR-7 expression through up-regulation of HuR in human lung cancer cells.
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DOI：
10.1186/1475-2867-13-90
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发表时间：
2013-09-03
影响因子：
5.8
通讯作者：
Xu L
中科院分区：
文献类型：
--
作者：
Li YJ;Wang CH;Zhou Y;Liao ZY;Zhu SF;Hu Y;Chen C;Luo JM;Wen ZK;Xu L
我们最近的证据表明Toll样受体9 （TLR9）信号可以通过抑制microRNA-7 （miR-7）的表达来增强人肺癌细胞的生长和转移潜能。人抗原R （Human antigen R, HuR）在细胞生物学中参与了多种mrna的稳定。然而，在TLR9信号刺激的人肺癌细胞中，HuR是否也导致了miR-7表达的改变还有待阐明。采用Real-time PCR和Western blot方法检测TLR9激动剂CpG寡核苷酸（ODNs）处理95D人肺癌细胞中HuR的表达。为了探讨HuR对miR-7表达的可能作用，我们将编码HuR的真核表达载体瞬时转染95D细胞，然后用Real-time PCR法检测miR-7的表达。采用RNA干扰、western blot、Real-time PCR、MTT法、BrdU标记法、侵袭法和划痕法检测HuR对CpG ODNs处理的人肺癌细胞中miR-7表达的破坏作用。最后，分别对PI3K、Akt或Erk进行抑制，并进行western blot，探索CpG ODNs处理的人肺癌细胞中与HuR表达相关的可能信号通路。我们的数据显示，TLR9激动剂CpG ODNs可以诱导人肺癌细胞中HuR的表达。此外，过表达HuR可降低肺癌细胞中miR-7的表达。值得注意的是，使用RNA干扰下调HuR可以恢复CpG ODNs处理的肺癌细胞中miR-7的表达，并伴有生长和转移潜力的增强。最后，CpG ODNs可通过Akt通路诱导HuR表达。我们的研究结果表明，在人肺癌细胞中，HuR可能作为调节因子调控TLR9信号相关的生物学效应，这可能有助于了解HuR在肿瘤生物学中的潜在作用。
Our recent evidence showed that Toll like receptor 9 (TLR9) signaling could enhance the growth and metastatic potential of human lung cancer cells through repressing microRNA-7 (miR-7) expression. Human antigen R (HuR) has been involved in stabilizing multiple mRNAs in cellular biology. However, whether HuR also contributed to the altered expression of miR-7 in TLR9 signaling stimulated human lung cancer cells remains to be elucidated. The expression of HuR in human lung cancer 95D cells treated with TLR9 agonist CpG Oligonucleotides (ODNs) was detected by Real-time PCR and Western blot assay. To explore the possible role of HuR on miR-7 expression, eukaryotic expression vector encoding HuR was transiently transfected into 95D cells and then the expression of miR-7 was detected by Real-time PCR assay. Moreover, RNA interference, western blot, Real-time PCR, MTT assay, BrdU labeling, invasion assay and scratch assay were employed to examine the disrupt effect of HuR on miR-7 expression in human lung cancer cells treated with CpG ODNs. Finally, inhibitors for PI3K, Akt or Erk respectively, and western blot were performed to explore the possible signaling pathway related to HuR expression in CpG ODNs treated human lung cancer cells. Our data showed that TLR9 agonist CpG ODNs could induce the expression of HuR in human lung cancer cells. Moreover, overexpression of HuR could reduce the expression of miR-7 in lung cancer cells. Notably, down-regulation of HuR using RNA interference restored miR-7 expression in CpG ODNs treated lung cancer cells, accompanied by enhanced growth and metastatic potential. Finally, CpG ODNs could induce HuR expression through Akt pathway. Our findings indicated that HuR could act as regulator in regulating TLR9 signaling associated biological effect in human lung cancer cells, which might be helpful for the understanding of the potential role of HuR in tumor biology.
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影响因子：
11.2
作者：
Reddy SD;Ohshiro K;Rayala SK;Kumar R
通讯作者：
Kumar R
影响因子：
8.8
作者：
Kurosu, T.;Ohga, N.;Hida, Y.;Maishi, N.;Akiyama, K.;Kakuguchi, W.;Kuroshima, T.;Kondo, M.;Akino, T.;Totsuka, Y.;Shindoh, M.;Higashino, F.;Hida, K.
通讯作者：
Hida, K.
DOI：
10.1016/j.bbrc.2009.03.072
发表时间：
2009-05-08
影响因子：
3.1
作者：
Xu, Lin;Zhou, Ya;Wen, Zhen-Ke
通讯作者：
Wen, Zhen-Ke
影响因子：
4.8
作者：
Webster, Rebecca J.;Giles, Keith M.;Leedman, Peter J.
通讯作者：
Leedman, Peter J.
影响因子：
5.8
作者：
Droemann D;Albrecht D;Gerdes J;Ulmer AJ;Branscheid D;Vollmer E;Dalhoff K;Zabel P;Goldmann T
通讯作者：
Goldmann T