Up-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling

Abstract The present study was designed to investigate the potential clinical, pathological, prognostic value, role and mechanism of BRCA1-associated RING Domain 1 (BARD1) in Hepatocellular carcinoma (HCC). Quantitative real-time PCR and immunohistochemistry were performed to evaluate the expression...

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Autores principales: Yan Liao, Shengguang Yuan, Xinhuang Chen, Pengpeng Zhu, Jun Li, Liling Qin, Weijia Liao
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/33cf714f74d24c2f8e600a36f69d5bc3
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spelling oai:doaj.org-article:33cf714f74d24c2f8e600a36f69d5bc32021-12-02T16:06:46ZUp-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling10.1038/s41598-017-07962-72045-2322https://doaj.org/article/33cf714f74d24c2f8e600a36f69d5bc32017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07962-7https://doaj.org/toc/2045-2322Abstract The present study was designed to investigate the potential clinical, pathological, prognostic value, role and mechanism of BRCA1-associated RING Domain 1 (BARD1) in Hepatocellular carcinoma (HCC). Quantitative real-time PCR and immunohistochemistry were performed to evaluate the expression of BARD1 mRNA and protein. The expression of BARD1 in the HCC tissue samples was markedly higher than that in the adjacent noncancerous liver tissues. Elevated BARD1 expression was positively correlated with tumor-node-metastasis stage, Barcelona-Clinic Liver Cancer stage, hepatitis B surface antigen, large tumor size, serum alpha-fetoprotein levels, and serum aspartate aminotransferase levels. Univariate and multivariate analyses revealed the BARD1 was an independent predictor for decreased progression-free survival and overall survival in HCC. In vitro experiments demonstrated that knocking down BARD1 significantly inhibited the proliferation, invasion and migration of HCC cells. Moreover, silencing BARD1 inhibit the signaling pathway via decreased the levels of Akt, mTOR, and MMP-9 and inhibited the phosphorylation of Akt (Ser473) and mTOR (Ser2248). Collectively, our findings suggest that BARD1 may be a novel diagnostic and prognostic biomarker of HCC, and up-regulation of BARD1 can contribute to HCC progression by targeting Akt signaling.Yan LiaoShengguang YuanXinhuang ChenPengpeng ZhuJun LiLiling QinWeijia LiaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yan Liao
Shengguang Yuan
Xinhuang Chen
Pengpeng Zhu
Jun Li
Liling Qin
Weijia Liao
Up-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling
description Abstract The present study was designed to investigate the potential clinical, pathological, prognostic value, role and mechanism of BRCA1-associated RING Domain 1 (BARD1) in Hepatocellular carcinoma (HCC). Quantitative real-time PCR and immunohistochemistry were performed to evaluate the expression of BARD1 mRNA and protein. The expression of BARD1 in the HCC tissue samples was markedly higher than that in the adjacent noncancerous liver tissues. Elevated BARD1 expression was positively correlated with tumor-node-metastasis stage, Barcelona-Clinic Liver Cancer stage, hepatitis B surface antigen, large tumor size, serum alpha-fetoprotein levels, and serum aspartate aminotransferase levels. Univariate and multivariate analyses revealed the BARD1 was an independent predictor for decreased progression-free survival and overall survival in HCC. In vitro experiments demonstrated that knocking down BARD1 significantly inhibited the proliferation, invasion and migration of HCC cells. Moreover, silencing BARD1 inhibit the signaling pathway via decreased the levels of Akt, mTOR, and MMP-9 and inhibited the phosphorylation of Akt (Ser473) and mTOR (Ser2248). Collectively, our findings suggest that BARD1 may be a novel diagnostic and prognostic biomarker of HCC, and up-regulation of BARD1 can contribute to HCC progression by targeting Akt signaling.
format article
author Yan Liao
Shengguang Yuan
Xinhuang Chen
Pengpeng Zhu
Jun Li
Liling Qin
Weijia Liao
author_facet Yan Liao
Shengguang Yuan
Xinhuang Chen
Pengpeng Zhu
Jun Li
Liling Qin
Weijia Liao
author_sort Yan Liao
title Up-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling
title_short Up-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling
title_full Up-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling
title_fullStr Up-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling
title_full_unstemmed Up-regulation of BRCA1-associated RING Domain 1 Promotes Hepatocellular Carcinoma Progression by Targeting Akt Signaling
title_sort up-regulation of brca1-associated ring domain 1 promotes hepatocellular carcinoma progression by targeting akt signaling
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/33cf714f74d24c2f8e600a36f69d5bc3
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