Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of, China.
Mol Carcinog. 2014 Apr;53(4):325-36. doi: 10.1002/mc.21981. Epub 2012 Nov 20.
We previously identified JWA as a novel microtubule-associated protein (MAP), which is implicated in carcinogenesis and tumor progression. The aims of the present study were to investigate the biological action and the prognostic significance of JWA in hepatocellular carcinoma (HCC). Quantitative real-time PCR and Western blot were used to detect JWA mRNA and protein expression, respectively, in stepwise metastatic HCC cell lines and HCC tissues. Short hairpin RNA was used to inhibit JWA expression in HCC cells. The effects of JWA depletion on cell migration, invasion, adhesion and in vivo metastasis were investigated. Immunohistochemistry of JWA was conducted in microarrays with tissue from 314 HCC patients who had undergone surgical resection. Prognostic significance was assessed using the Kaplan-Meier method and log-rank tests. The result showed JWA expression was decreased in the highly metastatic HCC cell lines and HCC tissues. Depletion of JWA caused a notable increase in cell migration, invasion and adhesion in vitro and metastasis in vivo. Furthermore, there was an inverse correlation between JWA expression and FAK expression and phosphorylation, RhoA activation and matrix metalloproteinase-2 (MMP-2) activity in HCC cells. More notably, multivariate analysis revealed that a low level of JWA expression was an independent prognosticator for both recurrence-free and overall survival for HCC patients after surgical resection, especially for AFP-normal HCC patients. Taken together, our data demonstrate that JWA plays a crucial role in HCC progression and suggest JWA may be a potential prognostic biomarker and therapeutic target for HCC.
我们之前已经鉴定出 JWA 是一种新型的微管相关蛋白（MAP），它与肿瘤发生和肿瘤进展有关。本研究的目的是研究 JWA 在肝细胞癌（HCC）中的生物学作用和预后意义。采用实时定量 PCR 和 Western blot 分别检测逐步转移的 HCC 细胞系和 HCC 组织中 JWA mRNA 和蛋白表达。用短发夹 RNA 抑制 HCC 细胞中的 JWA 表达。研究 JWA 耗竭对细胞迁移、侵袭、黏附和体内转移的影响。采用免疫组织化学方法对 314 例接受手术切除的 HCC 患者的组织芯片进行 JWA 检测。采用 Kaplan-Meier 法和对数秩检验评估预后意义。结果表明，JWA 在高转移性 HCC 细胞系和 HCC 组织中的表达降低。JWA 耗竭导致 HCC 细胞体外迁移、侵袭和黏附能力显著增强，体内转移能力增强。此外，JWA 表达与 FAK 表达和磷酸化、RhoA 激活以及基质金属蛋白酶-2（MMP-2）活性呈负相关。更重要的是，多因素分析表明，JWA 低表达是 HCC 患者手术切除后无复发生存和总生存的独立预后因素，尤其是对 AFP 正常的 HCC 患者。总之，我们的数据表明 JWA 在 HCC 进展中起关键作用，并提示 JWA 可能是 HCC 的潜在预后标志物和治疗靶点。
