POU2F1 over-expression correlates with poor prognoses and promotes cell growth and epithelial-to-mesenchymal transition in hepatocellular carcinoma.
POU2F1 over-expression correlates with poor prognoses and promotes cell growth and epithelial-to-mesenchymal transition in hepatocellular carcinoma.
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POU2F1 过度表达与不良预后相关，并促进肝细胞癌中的细胞生长和上皮间质转化。
DOI：
10.18632/oncotarget.17296
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发表时间：
2017-07-04
期刊：
影响因子：
--
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Zhong Y;Huang H;Chen M;Huang J;Wu Q;Yan GR;Chen D
尽管最近的努力，以了解POU结构域2类转录因子1（POU2F1）的活动，很少有人知道POU2F1在肝细胞癌（HCC）的肿瘤发生的作用及其与任何临床病理特征的HCC。在这项研究中，我们发现POU2F1在HCC标本中的表达明显高于邻近的非癌肝标本。POU2F1蛋白高表达与肿瘤体积大、组织学分级高、有无转移、临床分期高呈正相关，且POU2F1高表达的HCC患者预后差。我们进一步证明POU2F1过表达促进HCC细胞增殖、集落形成、上皮向间质转化（EMT）、迁移和侵袭，而POU2F1沉默抑制这些恶性表型。POU 2F1诱导参与EMT调节的Twist 1、Snai 1、Snai 2和ZEB 1基因的表达。此外，POU2F1在HCC中被AKT通路上调，并且POU2F1的过表达逆转了AKT敲低对HCC恶性表型的抑制，表明POU2F1是AKT通路的关键下游效应子。总的来说，我们的研究结果表明，POU 2F1过表达与肝癌患者的侵袭性表型和生存率低正相关，而AKT途径调节的POU 2F1通过调节EMT基因的转录促进肝癌侵袭性表型。POU2F1有可能成为肝癌新的预后因子和治疗靶点。
Despite recent efforts to understand activities of POU domain class 2 transcription factor 1 (POU2F1), little is known about the roles of POU2F1 in hepatocellular carcinoma (HCC) tumorigenesis and its correlation with any clinicopathological feature of HCC. In this study, we found that POU2F1 was significantly up-regulated in HCC specimens compared with adjacent non-cancerous liver specimens. The high POU2F1 protein expression level positively correlated with large tumor size, high histological grade, tumor metastasis and advanced clinical stage, and HCC patients with high POU2F1 levels exhibited poor prognoses. We further demonstrated that POU2F1 over-expression promoted HCC cell proliferation, colony formation, epithelial-to-mesenchymal transition (EMT), migration and invasion, while silencing of POU2F1 inhibited these malignant phenotypes. POU2F1 induced the expression of Twist1, Snai1, Snai2 and ZEB1 genes which are involved in the regulation of EMT. Furthermore, POU2F1 was up-regulated by AKT pathway in HCC, and POU2F1 over-expression reversed the inhibition of malignant phenotypes induced by AKT knock-down, indicating POU2F1 is a key down-stream effector of AKT pathway. Collectively, our results indicate that POU2F1 over-expression is positively associated with aggressive phenotypes and poor survival in patients with HCC, and POU2F1 regulated by AKT pathway promotes HCC aggressive phenotypes by regulating the transcription of EMT genes. POU2F1 may be employed as a new prognostic factor and therapeutic target for HCC.
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