Research Papers:

Regulation of migration and invasion by Toll-like receptor-9 signaling network in prostate cancer

Yun Luo _, Qi-Wei Jiang, Jie-Ying Wu, Jian-Ge Qiu, Wen-Ji Zhang, Xiao-Long Mei, Zhi Shi and Jin-Ming Di

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Oncotarget. 2015; 6:22564-22574. https://doi.org/10.18632/oncotarget.4197

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Yun Luo1,*, Qi-Wei Jiang2,*, Jie-Ying Wu1,*, Jian-Ge Qiu2, Wen-Ji Zhang2, Xiao-Long Mei2, Zhi Shi2, Jin-Ming Di1

1Department of Urology, The 3rd Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

2Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, China

*These authors have contributed equally to this work

Correspondence to:

Jin-Ming Di, e-mail: [email protected]

Zhi Shi, e-mail: [email protected]

Keywords: TLR9, migration, invasion, prostate cancer

Received: February 26, 2015     Accepted: May 23, 2015     Published: June 05, 2015


Toll-like receptors (TLRs) play an important role in tumorigenesis and progress of prostate cancer. However, the function and mechanism of Toll-like receptor-9 (TLR9) in prostate cancer is not totally understood. Here, we found that high expression of TLR9 was associated with a higher probability of lymph node metastasis and poor prognosis. Further in vitro functional study verified that silence of TLR9 inhibited migration and invasion of PC-3 cells, indicating expression of TLR9 involving in the migration and invasion of cancer cells. The data of microarray exhibited silence of TLR9 induced 205 genes with larger than 2-fold changes in expression levels, including 164 genes down-regulated and 41 genes up-regulated. Functional Gene Ontology (GO) processes annotation demonstrated that the top three scores of molecular and cellular functions were regulation of programmed cell death, regulation of locomotion and response to calcium ion. TLR9 signaling network analysis of the migration and invasion related genes identified several genes, like matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9), chemokine receptor 4 (CXCR4) and interleukin 8 (IL8), formed the core interaction network based on their known biological relationships. A few genes, such as odontogenic ameloblast-associated protein (ODAM), claudin 2 (CLDN2), gap junction protein beta 1 (GJB1) and Rho-associated coiled-coil containing protein kinase 1 pseudogene 1 (ROCK1P1), so far have not been found to interact with the other genes. This study provided the foundation to discover the new molecular mechanism in signaling networks of invasion and metastasis in prostate cancer.

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