Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China.
Disease Prevention and Control Center of Guilin, Guilin, Guangxi, P.R. China.
Sci Rep. 2017 Aug 9;7(1):7649. doi: 10.1038/s41598-017-07962-7.
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.
本研究旨在探讨 BRCA1 相关 RING 结构域 1（BARD1）在肝细胞癌（HCC）中的潜在临床、病理、预后价值、作用和机制。通过定量实时 PCR 和免疫组织化学检测 BARD1 mRNA 和蛋白的表达。结果显示，BARD1 在 HCC 组织样本中的表达明显高于相邻非癌性肝组织。BARD1 表达升高与肿瘤-淋巴结-转移分期、巴塞罗那临床肝癌分期、乙型肝炎表面抗原、大肿瘤大小、血清甲胎蛋白水平和血清天冬氨酸转氨酶水平呈正相关。单因素和多因素分析表明，BARD1 是 HCC 患者无进展生存期和总生存期的独立预测因子。体外实验表明，敲低 BARD1 可显著抑制 HCC 细胞的增殖、侵袭和迁移。此外，沉默 BARD1 可通过降低 Akt、mTOR 和 MMP-9 的水平，抑制 Akt（Ser473）和 mTOR（Ser2248）的磷酸化，从而抑制 Akt 信号通路。综上所述，我们的研究结果表明，BARD1 可能是 HCC 的一种新型诊断和预后生物标志物，上调 BARD1 可能通过靶向 Akt 信号通路促进 HCC 的进展。
