PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway
Prostate cancer is a serious disease that can invade bone tissues. These bone metastases can greatly decrease a patient’s quality of life, pose a financial burden, and even result in death. In recent years, tumor cell-secreted microvesicles have been identified and proposed to be a key factor in cel...
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Online Access: | http://dx.doi.org/10.1155/2019/8650846 |
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doaj-f8dcb2ae7d66473cb1f0b1cbec9c849b2020-11-25T01:49:06ZengHindawi LimitedBioMed Research International2314-61332314-61412019-01-01201910.1155/2019/86508468650846PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling PathwayYang Duan0Zhiwen Tan1Minsheng Yang2Jianjun Li3Chun Liu4Chengqiang Wang5Fu Zhang6Yanglei Jin7Yihan Wang8Lixin Zhu9Department of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Spinal Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaProstate cancer is a serious disease that can invade bone tissues. These bone metastases can greatly decrease a patient’s quality of life, pose a financial burden, and even result in death. In recent years, tumor cell-secreted microvesicles have been identified and proposed to be a key factor in cell interaction. However, the impact of cancer-derived exosomes on bone cells remains unclear. Herein, we isolated exosomes from prostate cancer cell line PC-3 and investigated their effects on human osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. The potential mechanism was evaluated by qRT-PCR, western blotting, and microRNA transfection experiments. The results showed that PC-3-derived exosomes dramatically inhibited osteoclast differentiation. Marker genes of mature osteoclasts, including CTSK, NFATc1, ACP5, and miR-214, were all downregulated in the presence of PC-3 exosomes. Furthermore, transfection experiments showed that miR-214 downregulation severely impaired osteoclast differentiation, whereas overexpression of miR-214 promoted differentiation. Furthermore, we demonstrated that PC-3-derived exosomes block the NF-κB signaling pathway. Our study suggested that PC-3-derived exosomes inhibit osteoclast differentiation by downregulating miR-214 and blocking the NF-κB signaling pathway. Therefore, elevating miR-214 levels in the bone metastatic site may attenuate the invasion of prostate cancer.http://dx.doi.org/10.1155/2019/8650846 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang Duan Zhiwen Tan Minsheng Yang Jianjun Li Chun Liu Chengqiang Wang Fu Zhang Yanglei Jin Yihan Wang Lixin Zhu |
spellingShingle |
Yang Duan Zhiwen Tan Minsheng Yang Jianjun Li Chun Liu Chengqiang Wang Fu Zhang Yanglei Jin Yihan Wang Lixin Zhu PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway BioMed Research International |
author_facet |
Yang Duan Zhiwen Tan Minsheng Yang Jianjun Li Chun Liu Chengqiang Wang Fu Zhang Yanglei Jin Yihan Wang Lixin Zhu |
author_sort |
Yang Duan |
title |
PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway |
title_short |
PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway |
title_full |
PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway |
title_fullStr |
PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway |
title_full_unstemmed |
PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway |
title_sort |
pc-3-derived exosomes inhibit osteoclast differentiation by downregulating mir-214 and blocking nf-κb signaling pathway |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2019-01-01 |
description |
Prostate cancer is a serious disease that can invade bone tissues. These bone metastases can greatly decrease a patient’s quality of life, pose a financial burden, and even result in death. In recent years, tumor cell-secreted microvesicles have been identified and proposed to be a key factor in cell interaction. However, the impact of cancer-derived exosomes on bone cells remains unclear. Herein, we isolated exosomes from prostate cancer cell line PC-3 and investigated their effects on human osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. The potential mechanism was evaluated by qRT-PCR, western blotting, and microRNA transfection experiments. The results showed that PC-3-derived exosomes dramatically inhibited osteoclast differentiation. Marker genes of mature osteoclasts, including CTSK, NFATc1, ACP5, and miR-214, were all downregulated in the presence of PC-3 exosomes. Furthermore, transfection experiments showed that miR-214 downregulation severely impaired osteoclast differentiation, whereas overexpression of miR-214 promoted differentiation. Furthermore, we demonstrated that PC-3-derived exosomes block the NF-κB signaling pathway. Our study suggested that PC-3-derived exosomes inhibit osteoclast differentiation by downregulating miR-214 and blocking the NF-κB signaling pathway. Therefore, elevating miR-214 levels in the bone metastatic site may attenuate the invasion of prostate cancer. |
url |
http://dx.doi.org/10.1155/2019/8650846 |
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