HMGB1 Promotes Prostate Cancer Development and Metastasis by Interacting with Brahma-Related Gene 1 and Activating the Akt Signaling Pathway

: We have previously shown that high-mobility group box 1 ( ) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of i...

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Veröffentlicht in:Theranostics 2019-01, Vol.9 (18), p.5166-5182
Hauptverfasser: Lv, Dao-Jun, Song, Xian-Lu, Huang, Bin, Yu, Yu-Zhong, Shu, Fang-Peng, Wang, Chong, Chen, Hong, Zhang, Hai-Bo, Zhao, Shan-Chao
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Sprache:eng
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Zusammenfassung:: We have previously shown that high-mobility group box 1 ( ) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of in PCa tumorigenesis. : Gain-of-function and loss-of-function experiments were used to determine the biological functions of both and . Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of and its relationship with Brahma-related gene 1 ( ) was examined by immunohistochemistry. : The results demonstrated that ectopic expression of facilitated growth and metastasis of PCa by enhancing signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of showed the opposite effects. Mechanistically, exerted these functions through its interaction with which may augment function and activate the signaling pathway thereby promoting EMT. Importantly, both and expression was markedly increased in human PCa tissues. : Taken together, these findings indicate that upregulation of promotes PCa development activation of and accelerates metastasis through regulating -mediated EMT. could be used as a novel potential target for the treatment of PCa.
ISSN:1838-7640
1838-7640
DOI:10.7150/thno.33972