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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Main Authors: Yang Duan, Zhiwen Tan, Minsheng Yang, Jianjun Li, Chun Liu, Chengqiang Wang, Fu Zhang, Yanglei Jin, Yihan Wang, Lixin Zhu
Format: Article
Language:English
Published: Hindawi Limited 2019-01-01
Series:BioMed Research International
Online Access:http://dx.doi.org/10.1155/2019/8650846
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spelling 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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