Oncotarget

Research Papers:

Exosomal miR-141-3p regulates osteoblast activity to promote the osteoblastic metastasis of prostate cancer

Yun Ye, Su-Liang Li, Yue-Yun Ma, Yan-Jun Diao, Liu Yang, Ming-Quan Su, Zhuo Li, Yang Ji, Juan Wang, Lin Lei, Wei-Xiao Fan, La-Xiu Li, Yi Xu and Xiao-Ke Hao _

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Oncotarget. 2017; 8:94834-94849. https://doi.org/10.18632/oncotarget.22014

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Abstract

Yun Ye1,2,*, Su-Liang Li2,*, Yue-Yun Ma1, Yan-Jun Diao1, Liu Yang1, Ming-Quan Su1, Zhuo Li2, Yang Ji3, Juan Wang1, Lin Lei1, Wei-Xiao Fan1, La-Xiu Li1, Yi Xu1 and Xiao-Ke Hao1

1Department of Laboratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi 710032, China

2Department of Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi 710077, China

3Department of Radiology, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi 710077, China

*These authors have contributed equally to this study

Correspondence to:

Xiao-Ke Hao, email: haoxkg@126.com

Keywords: exosome; miR-141-3p; DLC1; p38MAPK; osteoblast activity

Received: May 07, 2017    Accepted: September 05, 2017    Published: October 24, 2017

ABSTRACT

Exosomes from cancer cells, which contain microRNA and reach metastasis loci prior to cancer cells, stimulate the formation of a metastatic microenvironment. Previous studies have shown that exosomal miR-141-3p is associated with metastatic prostate cancer (PCa). However, the role and regulatory mechanism of miR-141-3p in the microenvironment of bone metastases require further study. In this study, we performed a series of experiments in vivo and in vitro to determine whether exosomal miR-141-3p from MDA PCa 2b cells regulates osteoblast activity to promote osteoblastic metastasis. We demonstrate that extracts obtained from cell culture supernatants contained exosomes and that miR-141-3p levels were significantly higher in MDA PCa 2b cell exosomes. Via confocal imaging, numerous MDA PCa 2b exosomes were observed to enter osteoblasts, and miR-141-3p was transferred to osteoblasts through MDA PCa 2b exosomes in vitro. Exosomal miR-141-3p from MDA PCa 2b promoted osteoblast activity and increased osteoprotegerin OPG expression. miR-141-3p suppressed the protein levels of the target gene DLC1, indicating its functional significance in activating the p38MAPK pathway. In animal experiments, exosomal miR-141-3p had bone-target specificity and promoted osteoblast activity. Mice injected with miR-141-3p-mimics exosomes developed apparent osteoblastic bone metastasis. Exosomal miR-141-3p from MDA PCa 2b cells promoted osteoblast activity and regulated the microenvironment of bone metastases, which plays an important role in the formation of bone metastases and osteogenesis damage in PCa. Clarifying the specific mechanism of bone metastasis will help generate new possibilities for the treatment of PCa.


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