Abstract
BackgroundOur 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.MethodsThe 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.ResultsOur 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.ConclusionOur 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.
Highlights
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 expression
TLR9 signaling enhanced the expression of Human antigen R (HuR) in human lung cancer cells To investigate the potential role of HuR on the expression of miR-7, we firstly detected the expression of HuR in CpG ODNs, TLR9 agonist, treated human lung cancer cells
We further demonstrated that TLR9 signaling could enhance the expression of HuR through Akt pathway, which reduce the expression of miR-7, suggesting that PI3K/ Akt pathway was important for the expression of HuR in cancer cells
Summary
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. Our most recent study showed that downregulation of intrinsic miR-7 was important for TLR9 signaling enhanced growth and metastatic potential of human lung cancer cells [16]. Recent evidence showed that Human antigen R (HuR), a posttranscriptional regulator of gene expression, played a key role in stabilizing multiple mRNAs in cellular biology [17,18,19]. Whether HuR was involved in the expression of miR-7 in TLR9 signaling treated lung cancer cells still remains to be elucidated. We carefully evaluated the potential role of HuR in the expression of miR-7 on TLR9 signaling treated human lung cancer cells
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