Author:
Li Yong-Ju,Wang Chun-Hong,Zhou Ya,Liao Zheng-Yuan,Zhu Shun-Fei,Hu Yan,Chen Chao,Luo Jun-Min,Wen Zhen-Ke,Xu Lin
Abstract
Abstract
Background
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.
Methods
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.
Results
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.
Conclusion
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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference31 articles.
1. Pinto A, Morello S, Sorrentino R: Lung cancer and toll-like receptors. Cancer Immunol Immunother. 2011, 60: 1211-1220. 10.1007/s00262-011-1057-8.
2. Droemann D, Albrecht D, Gerdes J, Ulmer AJ, Branscheid D, Vollmer E, Dalhoff K, Zabel P, Goldmann T: Human lung cancer cells express functionally active toll-like receptor 9. Respir Res. 2005, 6: 1-10.1186/1465-9921-6-1.
3. Ren T, Wen ZK, Liu ZM, Liang YJ, Guo ZL, Xu L: Functional expression of TLR9 is associated to the metastatic potential of human lung cancer cell. Cancer Biol Ther. 2007, 6: 1704-1709. 10.4161/cbt.6.11.4826.
4. Sorrentino R, Morello S, Giordano MG, Arra C, Maiolino P, Adcock IM, Pinto A: CpG-ODN increases the release of VEGF in a mouse model of lung carcinoma. Int J Cancer. 2011, 128: 2815-2822. 10.1002/ijc.25626.
5. Samara KD, Antoniou KM, Karagiannis K, Margaritopoulos G, Lasithiotaki I, Koutala E, Siafakas NM: Expression profiles of toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis. Int J Oncol. 2012, 40: 1397-1404.
Cited by
27 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献